[ { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hyz55-cqx24", "eprint_status": "archive", "datestamp": "2024-01-19 00:14:59", "lastmod": "2024-01-19 00:14:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Evans-Constantine-G", "name": { "family": "Evans", "given": "Constantine Glen" }, "orcid": "0000-0002-7053-1670" }, { "id": "O'Brien-Jackson", "name": { "family": "O'Brien", "given": "Jackson" }, "orcid": "0000-0002-5221-2107" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Murugan-Arvind", "name": { "family": "Murugan", "given": "Arvind" }, "orcid": "0000-0001-5464-917X" } ] }, "title": "Pattern recognition in the nucleation kinetics of non-equilibrium self-assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "Multidisciplinary", "note": "
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\n\nWe thank M. Brenner, J. Bruck, A. Dinner, D. Doty, D.K. Fygenson, S. Leibler, R.M. Murray, L. Qian, P.W.K. Rothemund, P. Šulc, C. Thachuk, G. Tikhomirov, D. Woods and Z. Zeravcic. T. Zhu, T. Ouldridge, S. Buse, M. Alexander, M. Misra and A. Lapteva also provided valuable feedback on early drafts. We thank Z. Zeravcic for assistance with artwork in Fig. 1. Funding: supported by National Science Foundation grant nos. CCF-1317694 and CCF/FET-2008589, the Evans Foundation for Molecular Medicine, European Research Council grant no. 772766, Science Foundation Ireland grant no. 18/ERCS/5746 and the Carver Mead New Adventures Fund. J.O.B. and A.M. were primarily supported by the University of Chicago Materials Research Science and Engineering Center, which is funded by National Science Foundation under award number DMR-2011854. A.M. acknowledges support from the Simons Foundation.
\nC.G.E., E.W. and A.M. conceived the study. C.G.E. and E.W. designed the molecules. C.G.E., J.O.B., E.W. and A.M. wrote simulation code, designed the experiments and performed the experiments, analysed the data and wrote the manuscript.
\n\nAFM images, fluorescence trajectories, DNA sequences and simulation results are available at https://www.dna.caltech.edu/SupplementaryMaterial/MultifariousSST/.
\n\nAlgorithms for tile set design, sequence design, nucleation rate prediction and pixel-to-tile map optimization are available at https://www.dna.caltech.edu/SupplementaryMaterial/MultifariousSST/.
\n\nThe authors declare no competing interests.
\nInspired by biology’s most sophisticated computer, the brain, neural networks constitute a profound reformulation of computational principles1,2,3. Analogous high-dimensional, highly interconnected computational architectures also arise within information-processing molecular systems inside living cells, such as signal transduction cascades and genetic regulatory networks4,5,6,7. Might collective modes analogous to neural computation be found more broadly in other physical and chemical processes, even those that ostensibly play non-information-processing roles? Here we examine nucleation during self-assembly of multicomponent structures, showing that high-dimensional patterns of concentrations can be discriminated and classified in a manner similar to neural network computation. Specifically, we design a set of 917 DNA tiles that can self-assemble in three alternative ways such that competitive nucleation depends sensitively on the extent of colocalization of high-concentration tiles within the three structures. The system was trained in silico to classify a set of 18 grayscale 30 × 30 pixel images into three categories. Experimentally, fluorescence and atomic force microscopy measurements during and after a 150 hour anneal established that all trained images were correctly classified, whereas a test set of image variations probed the robustness of the results. Although slow compared to previous biochemical neural networks, our approach is compact, robust and scalable. Our findings suggest that ubiquitous physical phenomena, such as nucleation, may hold powerful information-processing capabilities when they occur within high-dimensional multicomponent systems.
\nSubmitted - 2207.06399.pdf
", "abstract": "Inspired by biology's most sophisticated computer, the brain, neural networks constitute a profound reformulation of computational principles. Remarkably, analogous high-dimensional, highly-interconnected computational architectures also arise within information-processing molecular systems inside living cells, such as signal transduction cascades and genetic regulatory networks. Might neuromorphic collective modes be found more broadly in other physical and chemical processes, even those that ostensibly play non-information-processing roles such as protein synthesis, metabolism, or structural self-assembly? Here we examine nucleation during self-assembly of multicomponent structures, showing that high-dimensional patterns of concentrations can be discriminated and classified in a manner similar to neural network computation. Specifically, we design a set of 917 DNA tiles that can self-assemble in three alternative ways such that competitive nucleation depends sensitively on the extent of co-localization of high-concentration tiles within the three structures. The system was trained in-silico to classify a set of 18 grayscale 30 x 30 pixel images into three categories. Experimentally, fluorescence and atomic force microscopy monitoring during and after a 150-hour anneal established that all trained images were correctly classified, while a test set of image variations probed the robustness of the results. While slow compared to prior biochemical neural networks, our approach is surprisingly compact, robust, and scalable. This success suggests that ubiquitous physical phenomena, such as nucleation, may hold powerful information processing capabilities when scaled up as high-dimensional multicomponent systems.", "date": "2022-08-12", "date_type": "published", "publisher": "arXiv", "id_number": "CaltechAUTHORS:20220809-232339739", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220809-232339739", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF-2008589" }, { "agency": "Evans Foundation for Molecular Medicine" }, { "agency": "European Research Council (ERC)", "grant_number": "772766" }, { "agency": "Science Foundation Ireland", "grant_number": "18/ERCS/5746" }, { "agency": "Carver Mead New Adventures Fund" }, { "agency": "NSF", "grant_number": "DMR-2011854" }, { "agency": "Simons Foundation" } ] }, "doi": "10.48550/arXiv.2207.06399", "primary_object": { "basename": "2207.06399.pdf", "url": "https://authors.library.caltech.edu/records/x82d7-npr71/files/2207.06399.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Evans, Constantine Glen; O'Brien, Jackson; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7n39p-sdc71", "eprint_id": 106345, "eprint_status": "archive", "datestamp": "2023-08-22 07:56:51", "lastmod": "2023-10-20 23:22:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnson-R-F", "name": { "family": "Johnson", "given": "Robert F." }, "orcid": "0000-0002-5340-8347" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Verifying polymer reaction networks using bisimulation", "ispublished": "pub", "full_text_status": "public", "keywords": "Verification; Molecular computing; Bisimulation; Chemical Reaction Networks; Polymer Reaction Networks; DNA strand displacement", "note": "\u00a9 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). \n\nReceived 8 January 2020, Revised 6 August 2020, Accepted 10 August 2020, Available online 1 September 2020. \n\nThe authors would like to thank Chris Thachuk, Damien Woods, Dave Doty, Seung Woo Shin, and Lulu Qian for helpful discussions. RFJ and EW were supported by NSF grants 1317694, 1213127, and 0832824. RFJ was also supported by Caltech's Summer Undergraduate Research Fellowship and an NSF graduate fellowship. \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nPublished - 1-s2.0-S0304397520304473-main.pdf
", "abstract": "The Chemical Reaction Network model has been proposed as a programming language for molecular programming. Methods to implement arbitrary CRNs using DNA strand displacement circuits have been investigated, as have methods to prove the correctness of those or other implementations. However, the stochastic Chemical Reaction Network model is provably not deterministically Turing-universal, that is, it is impossible to create a stochastic CRN where a given output molecule is produced if and only if an arbitrary Turing machine accepts. A DNA stack machine that can simulate arbitrary Turing machines with minimal slowdown deterministically has been proposed, but it uses unbounded polymers that cannot be modeled as a Chemical Reaction Network. We propose an extended version of a Chemical Reaction Network that models unbounded linear polymers made from a finite number of monomers. This Polymer Reaction Network model covers the DNA stack machine, as well as copy-tolerant Turing machines and some examples from biochemistry. We adapt the bisimulation method of verifying DNA implementations of Chemical Reaction Networks to our model, and use it to prove the correctness of the DNA stack machine implementation. We define a subclass of single-locus Polymer Reaction Networks and show that any member of that class can be bisimulated by a network using only four primitives, suggesting a method of DNA implementation. Finally, we prove that deciding whether an implementation is a bisimulation is \u03a0\u2070\u2082-complete, and thus undecidable in the general case, although it is tractable in many special cases of interest. We hope that the ability to model and verify implementations of Polymer Reaction Networks will aid in the rational design of molecular systems.", "date": "2020-12-02", "date_type": "published", "publication": "Theoretical Computer Science", "volume": "843", "publisher": "Elsevier", "pagerange": "84-114", "id_number": "CaltechAUTHORS:20201029-152451680", "issn": "0304-3975", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201029-152451680", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "IIS-1213127" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" } ] }, "doi": "10.1016/j.tcs.2020.08.007", "primary_object": { "basename": "1-s2.0-S0304397520304473-main.pdf", "url": "https://authors.library.caltech.edu/records/7n39p-sdc71/files/1-s2.0-S0304397520304473-main.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Johnson, Robert F. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xzz32-1hg70", "eprint_id": 96621, "eprint_status": "archive", "datestamp": "2023-08-22 05:16:20", "lastmod": "2023-12-22 23:07:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Badelt-S", "name": { "family": "Badelt", "given": "Stefan" }, "orcid": "0000-0003-2636-5801" }, { "id": "Grun-C", "name": { "family": "Grun", "given": "Casey" } }, { "id": "Sarma-K-V", "name": { "family": "Sarma", "given": "Karthik V." } }, { "id": "Wolfe-B-R", "name": { "family": "Wolfe", "given": "Brian" } }, { "id": "Shin-Seung-Woo", "name": { "family": "Shin", "given": "Seung Woo" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures", "ispublished": "pub", "full_text_status": "public", "keywords": "molecular programming; dynamic DNA nanotechnology; chemical reaction networks", "note": "\u00a9 2020 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. \n\nManuscript received 17/12/2019; Manuscript accepted 21/04/2020; Published online 03/06/2020; Published in print 24/06/2020. \n\nThe authors thank Chris Thachuk, Niles Pierce, Andrew Phillips, Peng Yin, Dave Zhang and Justin Werfel for discussion and support. \n\nWe declare we have no competing interests. \n\nThis work was supported by the National Science Foundation grant nos. CCF-0832824 (The Molecular Programming Project), CCF/HCC-1213127, CHE/CCF-1643606 and CCF-1317694 (the Expedition in Computing on 'Molecular Programming Architectures, Abstractions, Algorithms and Applications') and by the Gordon and Betty Moore Foundation through grant no. GBMF2809 to the Caltech Programmable Molecular Technology Initiative. Funding for S.B. was, in part, provided by a postdoctoral fellowship from the Caltech Biology and Biological Engineering Division. C.G. received support from the NIH/NIGMS Medical Scientist Training Program training grant, T32GM007205. K.V.S. acknowledges support from NIH NCI F30CA210329 and the UCLA-Caltech Medical Scientist Training Program.\n\nPublished - rsif.2019.0866.pdf
Submitted - 1505.03738.pdf
", "abstract": "Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of 'domain-level' representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species.", "date": "2020-06-01", "date_type": "published", "publication": "Journal of the Royal Society Interface", "volume": "17", "number": "167", "publisher": "The Royal Society", "pagerange": "Art. No. 20190866", "id_number": "CaltechAUTHORS:20190621-092351430", "issn": "1742-5689", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190621-092351430", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1643606" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "Caltech Division of Biology and Biological Engineering" }, { "agency": "NIH", "grant_number": "T32GM007205" }, { "agency": "NIH", "grant_number": "NCI F30CA210329" }, { "agency": "UCLA-Caltech Medical Scientist Training Program" } ] }, "doi": "10.1098/rsif.2019.0866", "primary_object": { "basename": "1505.03738.pdf", "url": "https://authors.library.caltech.edu/records/xzz32-1hg70/files/1505.03738.pdf" }, "related_objects": [ { "basename": "rsif.2019.0866.pdf", "url": "https://authors.library.caltech.edu/records/xzz32-1hg70/files/rsif.2019.0866.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Badelt, Stefan; Grun, Casey; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/9eq07-4kq88", "eprint_id": 103599, "eprint_status": "archive", "datestamp": "2023-08-22 04:58:38", "lastmod": "2023-12-22 23:11:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Clamons-Samuel-E", "name": { "family": "Clamons", "given": "Samuel" }, "orcid": "0000-0002-7993-2278" }, { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Programming and simulating chemical reaction networks on a surface", "ispublished": "pub", "full_text_status": "public", "keywords": "nanotechnology; molecular programming; surface chemistry", "note": "\u00a9 2020 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. \n\nManuscript received 23/11/2019; Manuscript accepted 30/04/2020; Published online 27/05/2020; Published in print 27/05/2020. \n\nThe authors thank Philip F. Petersen, Matthew M. Cook, Andr\u00e1s Cook, Chigozie Nri, Adam Butler, Gokul Gowri, Wei Li, Robert F. Johnson, Stefan Badelt and Constantine G. Evans for discussion, feedback and encouragement. P.F.P. contributed several example surface CRN programs to the online simulator, and helped optimize the line-building example presented here. M.M.C. taught us about synchronization mechanisms for cellular automata. Kudos to molecular rugby team captains P.F.P., M.M.C., A.C., C.N., A.B., G.G., S.B., L.Q., S.C. and E.W. \n\nData accessibility: Simulator code, including examples used in this paper, can be found in the 'paper-release' branch of the GitHub repository at https://github.com/sclamons/surface_crns, a fork of which is also available from the DNA and Natural Algorithms Group on GitHub (https://github.com/DNA-and-Natural-Algorithms-Group). A browser interface to the simulator is also available, along with examples from this paper and others, at http://www.dna.caltech.edu/Surface_CRN_Simulator/. \n\nAuthors' contributions: S.C. wrote the simulation software and online interfaces used in this paper. L.Q. and E.W. conceived the study. All authors constructed examples and wrote and revised substantial portions of the manuscript. All authors gave final approval for publication and agree to be held accountable for the work performed therein. \n\nWe declare we have no competing interests. \n\nThis work was supported in part by NSF grant nos. CCF-1317694 to E.W. and L.Q., CCF-1813550 and CCF-1351081 to L.Q. S.C. was supported by the Human Frontiers Research Science Program and the Institute for Collaborative Biotechnologies through contract W911NF-19-D-0001 from the U.S. Army Research Office to Richard M. Murray.\n\nPublished - rsif.2019.0790.pdf
", "abstract": "Models of well-mixed chemical reaction networks (CRNs) have provided a solid foundation for the study of programmable molecular systems, but the importance of spatial organization in such systems has increasingly been recognized. In this paper, we explore an alternative chemical computing model introduced by Qian & Winfree in 2014, the surface CRN, which uses molecules attached to a surface such that each molecule only interacts with its immediate neighbours. Expanding on the constructions in that work, we first demonstrate that surface CRNs can emulate asynchronous and synchronous deterministic cellular automata and implement continuously active Boolean logic circuits. We introduce three new techniques for enforcing synchronization within local regions, each with a different trade-off in spatial and chemical complexity. We also demonstrate that surface CRNs can manufacture complex spatial patterns from simple initial conditions and implement interesting swarm robotic behaviours using simple local rules. Throughout all example constructions of surface CRNs, we highlight the trade-off between the ability to precisely place molecules and the ability to precisely control molecular interactions. Finally, we provide a Python simulator for surface CRNs with an easy-to-use web interface, so that readers may follow along with our examples or create their own su", "date": "2020-05-01", "date_type": "published", "publication": "Journal of the Royal Society Interface", "volume": "17", "number": "166", "publisher": "The Royal Society", "pagerange": "Art. No. 20190790", "id_number": "CaltechAUTHORS:20200601-105515948", "issn": "1742-5689", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200601-105515948", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF-1813550" }, { "agency": "NSF", "grant_number": "CCF-1351081" }, { "agency": "Human Frontier Science Program" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-19-D-0001" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1098/rsif.2019.0790", "pmcid": "PMC7276541", "primary_object": { "basename": "rsif.2019.0790.pdf", "url": "https://authors.library.caltech.edu/records/9eq07-4kq88/files/rsif.2019.0790.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Clamons, Samuel; Qian, Lulu; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1f9vj-0v377", "eprint_id": 96572, "eprint_status": "archive", "datestamp": "2023-08-22 03:31:44", "lastmod": "2023-10-20 21:18:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cappelletti-D", "name": { "family": "Cappelletti", "given": "Daniele" } }, { "id": "Ortiz-Mu\u00f1oz-A", "name": { "family": "Ortiz-Mu\u00f1oz", "given": "Andr\u00e9s" }, "orcid": "0000-0003-1824-3230" }, { "id": "Anderson-D-F", "name": { "family": "Anderson", "given": "David F." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Stochastic Chemical Reaction Networks for Robustly Approximating Arbitrary Probability Distributions", "ispublished": "pub", "full_text_status": "public", "keywords": "Stochastic chemical reaction networks; Approximation; Arbitrary distributions; Detailed balance; Robustness; Molecular computing", "note": "\u00a9 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). \n\nReceived 6 November 2018, Revised 12 June 2019, Accepted 8 August 2019, Available online 29 August 2019. \n\nThe current structure of the project was conceived when the four authors participated in the BIRS 5-day Workshop \"Mathematical Analysis of Biological Interaction Networks.\" Parts of the proofs for the present work were then completed while two of the authors were taking part in the AIM SQuaRE workshop \"Dynamical properties of deterministic and stochastic models of reaction networks.\" We thank the Banff International Research Station and the American Institute of Mathematics for making this possible. \n\nAnderson gratefully acknowledges support via the Army Research Office through grant W911NF-18-1-0324. Winfree gratefully acknowledges support via the National Science Foundation \"Expedition in Computing\" grant CCF-1317694. Cappelletti has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme grant agreement No. 743269 (CyberGenetics project). \n\nThis material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1745301. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nPublished - 1-s2.0-S030439751930502X-main.pdf
Submitted - 1810.02854.pdf
", "abstract": "We show that discrete distributions on the d-dimensional non-negative integer lattice can be approximated arbitrarily well via the marginals of stationary distributions for various classes of stochastic chemical reaction networks. We begin by providing a class of detailed balanced networks and prove that they can approximate any discrete distribution to any desired accuracy. However, these detailed balanced constructions rely on the ability to initialize a system precisely, and are therefore susceptible to perturbations in the initial conditions. We therefore provide another construction based on the ability to approximate point mass distributions and prove that this construction is capable of approximating arbitrary discrete distributions for any choice of initial condition. In particular, the developed models are ergodic, so their limit distributions are robust to a finite number of perturbations over time in the counts of molecules.", "date": "2020-01-01", "date_type": "published", "publication": "Theoretical Computer Science", "volume": "801", "publisher": "Elsevier", "pagerange": "64-95", "id_number": "CaltechAUTHORS:20190619-141711510", "issn": "0304-3975", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190619-141711510", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-18-1-0324" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "European Research Council (ERC)", "grant_number": "743269" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1745301" } ] }, "doi": "10.1016/j.tcs.2019.08.013", "primary_object": { "basename": "1-s2.0-S030439751930502X-main.pdf", "url": "https://authors.library.caltech.edu/records/1f9vj-0v377/files/1-s2.0-S030439751930502X-main.pdf" }, "related_objects": [ { "basename": "1810.02854.pdf", "url": "https://authors.library.caltech.edu/records/1f9vj-0v377/files/1810.02854.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Cappelletti, Daniele; Ortiz-Mu\u00f1oz, Andr\u00e9s; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/38h63-czk16", "eprint_id": 104900, "eprint_status": "archive", "datestamp": "2023-08-19 16:51:42", "lastmod": "2024-01-15 17:04:04", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Chemical Reaction Networks and Stochastic Local Search", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2019 Springer Nature Switzerland AG. \n\nFirst Online: 24 July 2019. \n\nThis work was supported in part by National Science Foundation (NSF) grant 1317694 \u2013 The Molecular Programming Project. Thanks to Matt Cook, David Soloveichik, Chris Thachuk, William Poole, Lulu Qian, Grzegorz Rozenberg, Moshe Vardi, Tony Rojko, and Henry Lester for stimulating questions, comments, and encouragement.", "abstract": "Stochastic local search can be an effective method for solving a wide variety of optimization and constraint satisfaction problems. Here I show that some stochastic local search algorithms map naturally to stochastic chemical reaction networks. This connection highlights new ways in which stochasticity in chemical reaction networks can be used for search and thus for finding solutions to problems. The central example is a chemical reaction network construction for solving Boolean formula satisfiability problems. Using an efficient general-purpose stochastic chemical reaction network simulator, I show that direct simulation of the networks proposed here can be more efficient, in wall-clock time, than a somewhat outdated but industrial-strength commercial satisfiability solver. While not of use for practical computing, the constructions emphasize that exploiting the stochasticity inherent in chemical reaction network dynamics is not inherently inefficient \u2013 and indeed I propose that stochastic local search could be an important aspect of biological computation and should be exploited when engineering future artificial cells.", "date": "2019-07-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "1-20", "id_number": "CaltechAUTHORS:20200810-152243847", "isbn": "978-3-030-26806-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200810-152243847", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "contributors": { "items": [ { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" } } ] }, "doi": "10.1007/978-3-030-26807-7_1", "resource_type": "book_section", "pub_year": "2019", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pfxa8-yma36", "eprint_id": 104916, "eprint_status": "archive", "datestamp": "2023-08-19 16:51:50", "lastmod": "2024-01-15 17:04:06", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zolaktaf-S", "name": { "family": "Zolaktaf", "given": "Sedigheh" } }, { "id": "Dannenberg-F", "name": { "family": "Dannenberg", "given": "Frits" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bouchard-C\u00f4t\u00e9-A", "name": { "family": "Bouchard-C\u00f4t\u00e9", "given": "Alexandre" } }, { "id": "Schmidt-Mark", "name": { "family": "Schmidt", "given": "Mark" } }, { "id": "Condon-A", "name": { "family": "Condon", "given": "Anne" } } ] }, "title": "Efficient Parameter Estimation for DNA Kinetics Modeled as Continuous-Time Markov Chains", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2019 Springer Nature Switzerland AG. \n\nFirst Online: 24 July 2019.", "abstract": "Nucleic acid kinetic simulators aim to predict the kinetics of interacting nucleic acid strands. Many simulators model the kinetics of interacting nucleic acid strands as continuous-time Markov chains (CTMCs). States of the CTMCs represent a collection of secondary structures, and transitions between the states correspond to the forming or breaking of base pairs and are determined by a nucleic acid kinetic model. The number of states these CTMCs can form may be exponentially large in the length of the strands, making two important tasks challenging, namely, mean first passage time (MFPT) estimation and parameter estimation for kinetic models based on MFPTs. Gillespie's stochastic simulation algorithm (SSA) is widely used to analyze nucleic acid folding kinetics, but could be computationally expensive for reactions whose CTMC has a large state space or for slow reactions. It could also be expensive for arbitrary parameter sets that occur in parameter estimation. Our work addresses these two challenging tasks, in the full state space of all non-pseudoknotted secondary structures of each reaction. In the first task, we show how to use a reduced variance stochastic simulation algorithm (RVSSA), which is adapted from SSA, to estimate the MFPT of a reaction's CTMC. In the second task, we estimate model parameters based on MFPTs. To this end, first, we show how to use a generalized method of moments (GMM) approach, where we minimize a squared norm of moment functions that we formulate based on experimental and estimated MFPTs. Second, to speed up parameter estimation, we introduce a fixed path ensemble inference (FPEI) approach, that we adapt from RVSSA. We implement and evaluate RVSSA and FPEI using the Multistrand kinetic simulator. In our experiments on a dataset of DNA reactions, FPEI speeds up parameter estimation compared to inference using SSA, by more than a factor of three for slow reactions. Also, for reactions with large state spaces, it speeds up parameter estimation by more than a factor of two.", "date": "2019-07-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "80-99", "id_number": "CaltechAUTHORS:20200811-134907797", "isbn": "978-3-030-26806-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200811-134907797", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" } } ] }, "doi": "10.1007/978-3-030-26807-7_5", "resource_type": "book_section", "pub_year": "2019", "author_list": "Zolaktaf, Sedigheh; Dannenberg, Frits; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5bxzs-r2p68", "eprint_id": 97512, "eprint_status": "archive", "datestamp": "2023-08-19 16:51:35", "lastmod": "2024-01-14 21:51:24", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brailovskaya-T", "name": { "family": "Brailovskaya", "given": "Tatiana" } }, { "id": "Gowri-G", "name": { "family": "Gowri", "given": "Gokul" } }, { "id": "Yu-Sean", "name": { "family": "Yu", "given": "Sean" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Reversible Computation Using Swap Reactions on a Surface", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2019 Springer Nature Switzerland AG. \n\nFirst Online: 24 July 2019. \n\nT. Brailovskaya, G. Gowri and S. Yu\u2014Equal contribution. \n\nSupport from National Science Foundation grant CCF-1317694 is gratefully acknowledged. We also thank Lulu Qian and Chris Thachuk for helpful discussion and comments.", "abstract": "Chemical reaction networks (CRNs) and DNA strand displacement systems have shown potential for implementing logically and physically reversible computation. It has been shown that CRNs on a surface allow highly scalable and parallelizable computation. In this paper, we demonstrate that simple rearrangement reactions on a surface, which we refer to as swaps, are capable of physically reversible Boolean computation. We present designs for elementary logic gates, a method for constructing arbitrary feedforward digital circuits, and a proof of their correctness.", "date": "2019-07-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "174-196", "id_number": "CaltechAUTHORS:20190730-094203386", "isbn": "978-3-030-26806-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190730-094203386", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "contributors": { "items": [ { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" } } ] }, "doi": "10.1007/978-3-030-26807-7_10", "resource_type": "book_section", "pub_year": "2019", "author_list": "Brailovskaya, Tatiana; Gowri, Gokul; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b8q87-by423", "eprint_id": 96464, "eprint_status": "archive", "datestamp": "2023-08-22 01:25:26", "lastmod": "2023-10-20 21:12:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnson-Robert", "name": { "family": "Johnson", "given": "Robert" }, "orcid": "0000-0002-5340-8347" }, { "id": "Dong-Qing", "name": { "family": "Dong", "given": "Qing" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Verifying chemical reaction network implementations: A bisimulation approach", "ispublished": "pub", "full_text_status": "public", "keywords": "Chemical reaction networks; Formal verification; Bisimulation; Complexity theory", "note": "\u00a92018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). \n\nReceived 28 March 2017, Revised 23 December 2017, Accepted 4 January 2018, Available online 6 January 2018. \n\nThe authors would like to thank Chris Thachuk, Damien Woods, Dave Doty, and Seung Woo Shin for helpful discussions. We would also like to thank the anonymous reviewers for many helpful suggestions. RFJ and EW were supported by NSF grants 1317694, 1213127, and 0832824. RFJ was supported by Caltech's Summer Undergraduate Research Fellowship program and an NSF graduate fellowship. QD thanks Steve Skiena for his kindness and flexibility.\n\nPublished - 1-s2.0-S0304397518300136-main.pdf
", "abstract": "Efforts in programming DNA and other biological molecules have recently focused on general schemes to physically implement arbitrary Chemical Reaction Networks. Errors in some of the proposed schemes have driven a desire for formal verification methods. By interpreting each implementation species as a multiset of formal species, the concept of weak bisimulation can be adapted to CRNs in a way that agrees with an intuitive notion of a correct implementation. The theory of CRN bisimulation can be used to prove the correctness of a general implementation scheme or to detect subtle problems. Given a specific formal CRN and a specific implementation CRN, the complexity of finding a valid interpretation between the two CRNs if one exists, and that of checking whether an interpretation is valid are both PSPACE-complete in the general case, but are NP-complete and polynomial-time respectively under an assumption that holds in many cases of interest. We present effective algorithms for both of those problems. We further discuss features of CRN bisimulation including a transitivity property and a modularity condition, the precise connection to the general theory of bisimulation, and an extension that takes into account spurious catalysts.", "date": "2019-04-18", "date_type": "published", "publication": "Theoretical Computer Science", "volume": "765", "publisher": "Elsevier", "pagerange": "3-46", "id_number": "CaltechAUTHORS:20190617-104717955", "issn": "0304-3975", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190617-104717955", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "doi": "10.1016/j.tcs.2018.01.002", "primary_object": { "basename": "1-s2.0-S0304397518300136-main.pdf", "url": "https://authors.library.caltech.edu/records/b8q87-by423/files/1-s2.0-S0304397518300136-main.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Johnson, Robert; Dong, Qing; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/d9h3w-7mw95", "eprint_id": 96465, "eprint_status": "archive", "datestamp": "2023-08-22 01:25:33", "lastmod": "2023-10-20 21:12:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shin-Seung-Woo", "name": { "family": "Shin", "given": "Seung Woo" } }, { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Verifying chemical reaction network implementations: A pathway decomposition approach", "ispublished": "pub", "full_text_status": "public", "keywords": "Chemical reaction networks; Molecular computing; DNA computing; Formal verification; Molecular programming; Automated design", "note": "\u00a92017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). \n\nReceived 1 November 2014, Revised 2 October 2017, Accepted 13 October 2017, Available online 31 October 2017. \n\nWe appreciate helpful discussions with John Baez, Luca Cardelli, Vincent Danos, Qing Dong, Robert Johnson, Stefan Badelt, and Matthew Lakin. S.W.S. was supported by California Institute of Technology's Summer Undergraduate Research Fellowship 2009, NSF grant CCF-0832824, ARO Grant W911NF-09-1-0440 and NSF Grant CCF-0905626. C.T. was supported by NSF grants CCF-1213127, SHF-1718938, and a Banting Fellowship. E.W. was supported by NSF grants CCF-0832824, CCF-1213127, and CCF-1317694.\n\nPublished - 1-s2.0-S0304397517307399-main.pdf
Submitted - 1411.0782.pdf
", "abstract": "The emerging fields of genetic engineering, synthetic biology, DNA computing, DNA nanotechnology, and molecular programming herald the birth of a new information technology that acquires information by directly sensing molecules within a chemical environment, stores information in molecules such as DNA, RNA, and proteins, processes that information by means of chemical and biochemical transformations, and uses that information to direct the manipulation of matter at the nanometer scale. To scale up beyond current proof-of-principle demonstrations, new methods for managing the complexity of designed molecular systems will need to be developed. Here we focus on the challenge of verifying the correctness of molecular implementations of abstract chemical reaction networks, where operation in a well-mixed \"soup\" of molecules is stochastic, asynchronous, concurrent, and often involves multiple intermediate steps in the implementation, parallel pathways, and side reactions. This problem relates to the verification of Petri nets, but existing approaches are not sufficient for providing a single guarantee covering an infinite set of possible initial states (molecule counts) and an infinite state space potentially explored by the system given any initial state. We address these issues by formulating a new theory of pathway decomposition that provides an elegant formal basis for comparing chemical reaction network implementations, and we present an algorithm that computes this basis. Our theory naturally handles certain situations that commonly arise in molecular implementations, such as what we call \"delayed choice,\" that are not easily accommodated by other approaches. We further show how pathway decomposition can be combined with weak bisimulation to handle a wider class that includes most currently known enzyme-free DNA implementation techniques. We anticipate that our notion of logical equivalence between chemical reaction network implementations will be valuable for other molecular implementations such as biochemical enzyme systems, and perhaps even more broadly in concurrency theory.", "date": "2019-04-18", "date_type": "published", "publication": "Theoretical Computer Science", "volume": "765", "publisher": "Elsevier", "pagerange": "67-96", "id_number": "CaltechAUTHORS:20190617-104718056", "issn": "0304-3975", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190617-104718056", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-09-1-0440" }, { "agency": "NSF", "grant_number": "CCF-0905626" }, { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1718938" }, { "agency": "National Research Council of Canada" }, { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "doi": "10.1016/j.tcs.2017.10.011", "primary_object": { "basename": "1-s2.0-S0304397517307399-main.pdf", "url": "https://authors.library.caltech.edu/records/d9h3w-7mw95/files/1-s2.0-S0304397517307399-main.pdf" }, "related_objects": [ { "basename": "1411.0782.pdf", "url": "https://authors.library.caltech.edu/records/d9h3w-7mw95/files/1411.0782.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Shin, Seung Woo; Thachuk, Chris; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pqt1c-h4948", "eprint_id": 91684, "eprint_status": "archive", "datestamp": "2023-08-22 01:11:16", "lastmod": "2023-10-23 16:09:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Woods-Damien", "name": { "family": "Woods", "given": "Damien" } }, { "id": "Doty-D", "name": { "family": "Doty", "given": "David" }, "orcid": "0000-0002-3922-172X" }, { "id": "Myhrvold-C", "name": { "family": "Myhrvold", "given": "Cameron" } }, { "id": "Hui-Joy", "name": { "family": "Hui", "given": "Joy" } }, { "id": "Zhou-Felix", "name": { "family": "Zhou", "given": "Felix" } }, { "id": "Yin-Peng", "name": { "family": "Yin", "given": "Peng" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Diverse and robust molecular algorithms using reprogrammable DNA self-assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "Computer science; DNA computing", "note": "\u00a9 2019 Springer Nature Publishing AG. \n\nReceived 22 May 2018; Accepted 07 January 2019; Published 20 March 2019; Issue Date 21 March 2019. \n\nWe thank C. Evans, A. Gopinath, B. Wei, C. Geary, S. Woo, P. Rothemund and Y. Rondelez for experimental advice; R. Barish for contributing to preliminary designs for algorithmic self-assembly by SST; C. Moore, T. St\u00e9rin, C. Thachuk, P.-\u00c9. Meunier and C. Geary for discussions on theory; and L. Qian, G. Tikhomirov and P. Petersen for AFM usage. This work was supported by National Science Foundation (NSF) grants CCF-1162589 (to E.W., D.D. and D.W.), CCF-1162459 (to P.Y.), CCF-1219274 (to D.W. and D.D.), CCF-1619343 (to D.D.), CCF-0832824 and CCF-1317694 (Expeditions in Computing, to E.W.) and CCF-1317291 (Expeditions in Computing, to P.Y.), and by NASA grant NNX13AJ56G (to D.W.). C.M. was funded by the Fannie and John Hertz Foundation. F.Z. and J.H. received support from the Caltech Summer Undergraduate Research Fellowship program. \n\nAuthor Contributions: D.W., D.D., E.W. and P.Y. conceived the study. D.W., D.D. and E.W. designed the circuits and wrote the manuscript. D.W. and D.D. carried out all data analysis and experiments reported except for the nanotube nucleation/melt experiments (which were performed by J.H. and D.W.) and the unzipping and other early experimental protocols (performed by F.Z., C.M. and D.D.). \n\nCompeting interests: D.W., D.D., J.H., F.Z. and E.W. declare that they have no competing interests. P.Y. and C.M. declare competing interests: they are both listed as inventors on pending and issued patents on single-stranded tiles; and P.Y. is a co-founder of Ultivue Inc. and NuProbe Global.\n\nIn Fig. 1 of this Letter, prime symbols were erroneously included in some labels in panels c and d. In the bottom section of panel c, in the diagram beneath 'SST self-assembly', the labels w2a\u2032, w3a\u2032, w4a\u2032 and w5a\u2032 should read w2a, w3a, w4a and w5a, respectively. Similarly, in panel d, the labels w2a\u2032 and w3a\u2032 should read w2a and w3a, respectively. Additionally, there were some omissions in the Acknowledgements: R. Schulman should have been thanked for experimental advice, and R. Hariadi for contributing to preliminary designs for algorithmic self-assembly by SST. Finally, in Supplementary Figs. 8 and 9, the rightmost labels s should read s\u2032, and on page 64 of the Supplementary Information a citation to Telser et al. (1989) was missing and has been added as ref. 89; the subsequent citations have been renumbered. The Supplementary Information has been updated accordingly, and minor changes have also been made to the phrasing throughout to improve clarity. The original, incorrect version of the Supplementary Information is included as Supplementary Information to this Amendment, for transparency. The original Letter has been corrected online.\n\nSupplemental Material - 41586_2019_1014_MOESM1_ESM.pdf
Supplemental Material - 41586_2019_1014_MOESM2_ESM.pdf
Supplemental Material - 41586_2019_1014_MOESM3_ESM.pdf
", "abstract": "Molecular biology provides an inspiring proof-of-principle that chemical systems can store and process information to direct molecular activities such as the fabrication of complex structures from molecular components. To develop information-based chemistry as a technology for programming matter to function in ways not seen in biological systems, it is necessary to understand how molecular interactions can encode and execute algorithms. The self-assembly of relatively simple units into complex products is particularly well suited for such investigations. Theory that combines mathematical tiling and statistical\u2013mechanical models of molecular crystallization has shown that algorithmic behaviour can be embedded within molecular self-assembly processes, and this has been experimentally demonstrated using DNA nanotechnology with up to 22 tile types. However, many information technologies exhibit a complexity threshold\u2014such as the minimum transistor count needed for a general-purpose computer\u2014beyond which the power of a reprogrammable system increases qualitatively, and it has been unclear whether the biophysics of DNA self-assembly allows that threshold to be exceeded. Here we report the design and experimental validation of a DNA tile set that contains 355 single-stranded tiles and can, through simple tile selection, be reprogrammed to implement a wide variety of 6-bit algorithms. We use this set to construct 21 circuits that execute algorithms including copying, sorting, recognizing palindromes and multiples of 3, random walking, obtaining an unbiased choice from a biased random source, electing a leader, simulating cellular automata, generating deterministic and randomized patterns, and counting to 63, with an overall per-tile error rate of less than 1 in 3,000. These findings suggest that molecular self-assembly could be a reliable algorithmic component within programmable chemical systems. The development of molecular machines that are reprogrammable\u2014at a high level of abstraction and thus without requiring knowledge of the underlying physics\u2014will establish a creative space in which molecular programmers can flourish.", "date": "2019-03-21", "date_type": "published", "publication": "Nature", "volume": "567", "number": "3", "publisher": "Nature Publishing Group", "pagerange": "366-372", "id_number": "CaltechAUTHORS:20181211-124932769", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181211-124932769", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1162589" }, { "agency": "NSF", "grant_number": "CCF-1162459" }, { "agency": "NSF", "grant_number": "CCF-1219274" }, { "agency": "NSF", "grant_number": "CCF-1619343" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF-1317291" }, { "agency": "NASA", "grant_number": "NNX13AJ56G" }, { "agency": "Fannie and John Hertz Foundation" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" } ] }, "doi": "10.1038/s41586-019-1014-9", "primary_object": { "basename": "41586_2019_1014_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/pqt1c-h4948/files/41586_2019_1014_MOESM3_ESM.pdf" }, "related_objects": [ { "basename": "41586_2019_1014_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/pqt1c-h4948/files/41586_2019_1014_MOESM1_ESM.pdf" }, { "basename": "41586_2019_1014_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/pqt1c-h4948/files/41586_2019_1014_MOESM2_ESM.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Woods, Damien; Doty, David; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0s4hg-g5w93", "eprint_id": 91842, "eprint_status": "archive", "datestamp": "2023-08-22 00:30:11", "lastmod": "2023-10-19 23:46:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wang-Boya", "name": { "family": "Wang", "given": "Boya" } }, { "id": "Thachuk-Chris", "name": { "family": "Thachuk", "given": "Chris" }, "orcid": "0000-0001-5913-1732" }, { "id": "Ellington-Andrew-D", "name": { "family": "Ellington", "given": "Andrew D." }, "orcid": "0000-0001-6246-5338" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Soloveichik-David", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" } ] }, "title": "Effective design principles for leakless strand displacement systems", "ispublished": "pub", "full_text_status": "public", "keywords": "molecular programming; DNA strand displacement cascades; robustness; leak", "note": "\u00a9 2018 National Academy of Sciences. Published under the PNAS license. \n\nEdited by Ronald R. Breaker, Yale University, New Haven, CT, and approved November 9, 2018 (received for review April 20, 2018). PNAS published ahead of print December 13, 2018. \n\nB.W. and D.S. were supported by NSF Grants CCF-1618895 and CCF-1652824. C.T. and E.W. acknowledge support from NSF Grants CCF/HCC-1213127, CCF-1317694, and CCF/SHF-1718938 and the Gordon and Betty Moore Foundation's Programmable Molecular Technology Initiative. C.T. also thanks the Natural Sciences and Engineering Research Council of Canada for a Banting Fellowship. A.D.E. was supported by NSF Grant DBI-0939454, International Funding Agency Grant ERASynBio 1541244, and Welch Foundation Grant F-1654. \n\nAuthor contributions: B.W., C.T., E.W., and D.S. designed research; B.W. performed research; B.W., C.T., A.D.E., E.W., and D.S. analyzed data; and B.W., C.T., E.W., and D.S. wrote the paper. \n\nThe authors declare no conflict of interests. \n\nThis article is a PNAS Direct Submission. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1806859115/-/DCSupplemental.\n\nPublished - E12182.full.pdf
Supplemental Material - pnas.1806859115.sapp.pdf
", "abstract": "Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core \"translator\" component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.", "date": "2018-12-26", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "number": "52", "publisher": "National Academy of Sciences", "pagerange": "E12182-E12191", "id_number": "CaltechAUTHORS:20181213-151040513", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181213-151040513", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1618895" }, { "agency": "NSF", "grant_number": "CCF-1652824" }, { "agency": "NSF", "grant_number": "CCF/HCC-1213127" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF/SHF-1718938" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "NSF", "grant_number": "DBI-0939454" }, { "agency": "ERASynBio", "grant_number": "1541244" }, { "agency": "Robert A. Welch Foundation", "grant_number": "F-1654" } ] }, "doi": "10.1073/pnas.1806859115", "pmcid": "PMC6310779", "primary_object": { "basename": "E12182.full.pdf", "url": "https://authors.library.caltech.edu/records/0s4hg-g5w93/files/E12182.full.pdf" }, "related_objects": [ { "basename": "pnas.1806859115.sapp.pdf", "url": "https://authors.library.caltech.edu/records/0s4hg-g5w93/files/pnas.1806859115.sapp.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Wang, Boya; Thachuk, Chris; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/x2aq5-g3803", "eprint_id": 92906, "eprint_status": "archive", "datestamp": "2023-08-19 13:10:46", "lastmod": "2023-12-22 23:07:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Berleant-J", "name": { "family": "Berleant", "given": "Joseph" }, "orcid": "0000-0001-5672-4292" }, { "id": "Berlind-C", "name": { "family": "Berlind", "given": "Christopher" } }, { "id": "Badelt-S", "name": { "family": "Badelt", "given": "Stefan" } }, { "id": "Dannenberg-F", "name": { "family": "Dannenberg", "given": "Frits" } }, { "id": "Schaeffer-J", "name": { "family": "Schaeffer", "given": "Joseph" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA strand displacement, formal verification, nucleic acid secondary structure, kinetics, thermodynamics", "note": "\u00a9 2018 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution\nLicense http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. \n\nManuscript received 11/02/2018; Manuscript accepted 05/11/2018; Published online 19/12/2018; Published in print 12/2018. \n\nData accessibility: This article has no additional data. \n\nAuthors' contributions: J.B. helped design the analysis framework, helped create the Python implementation, performed data collection and data analysis, and wrote the manuscript; C.B. helped design the analysis framework and helped create the Python implementation; S.B. helped perform data collection and data analysis; F.D. assisted with the Multistrand back-end and rate formula derivations; J.S. helped design the analysis framework and gave guidance during its implementation; E.W. conceived of and designed the framework, helped with its implementation, and helped perform data collection and data analysis. All authors helped draft the manuscript and gave final approval for publication. \n\nWe declare that we have no competing interests. \n\nThis research was funded by NSF grant nos. CCF/HCC-1213127, CHE/CCF-1643606 and CCF-1317694 (the Expedition in Computing on 'Molecular Programming Architectures, Abstractions, Algorithms, and Applications') and by the Gordon and Betty Moore Foundation through grant no. GBMF2809 to the Caltech Programmable Molecular Technology Initiative. Funding for J.B. was in part provided by the NSF grant no. CCF-1564025 to Mark Bathe and by an NSF Graduate Research Fellowship. Funding for S.B. was in part provided by a postdoctoral fellowship from the Caltech Biology and Biological Engineering Division. \n\nThe authors appreciate discussion and guidance from Niranjan Srinivas and Chris Thachuk.\n\nPublished - rsif.2018.0107.pdf
Supplemental Material - rsif20180107supp1.pdf
", "abstract": "As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson\u2013Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simplicity permits using functional sections of each strand, called domains, without considering particular nucleotide sequences. However, the actual sequences used may have interactions not predicted at the domain-level abstraction, and new rigorous analysis techniques are needed to determine the extent to which the chosen sequences conform to the system's domain-level description. We have developed a computational method for verifying sequence-level systems by identifying discrepancies between the domain-level and sequence-level behaviour. This method takes a DNA system, as specified using the domain-level tool Peppercorn, and analyses data from the stochastic sequence-level simulator Multistrand and sequence-level thermodynamic analysis tool NUPACK to estimate important aspects of the system, such as reaction rate constants and secondary structure formation. These techniques, implemented as the Python package KinDA, will allow researchers to predict the kinetic and thermodynamic behaviour of domain-level systems after sequence assignment, as well as to detect violations of the intended behaviour.", "date": "2018-12-05", "date_type": "published", "publication": "Journal of the Royal Society Interface", "volume": "15", "number": "149", "publisher": "The Royal Society", "pagerange": "Art. No. 20180107", "id_number": "CaltechAUTHORS:20190213-154533494", "issn": "1742-5689", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190213-154533494", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1643606" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "NSF", "grant_number": "CCF-1564025" }, { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Caltech Division of Biology and Biological Engineering" } ] }, "doi": "10.1098/rsif.2018.0107", "primary_object": { "basename": "rsif.2018.0107.pdf", "url": "https://authors.library.caltech.edu/records/x2aq5-g3803/files/rsif.2018.0107.pdf" }, "related_objects": [ { "basename": "rsif20180107supp1.pdf", "url": "https://authors.library.caltech.edu/records/x2aq5-g3803/files/rsif20180107supp1.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Berleant, Joseph; Berlind, Christopher; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/txa7d-9ka65", "eprint_id": 104917, "eprint_status": "archive", "datestamp": "2023-08-19 11:25:42", "lastmod": "2024-01-15 17:04:08", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Evans-C-G", "name": { "family": "Evans", "given": "Constantine G." }, "orcid": "0000-0002-7053-1670" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Optimizing Tile Set Size While Preserving Proofreading with a DNA Self-assembly Compiler", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2018 Springer Nature Switzerland AG. \n\nFirst Online: 07 September 2018. \n\nWe thank Chigozie Nri, Philip Petersen, Lulu Qian, and Grigory Tikhomirov for discussions and collaboration on physical implementations and the Alhambra compiler, and Robert Johnson and William Poole for discussions on aTAM equivalence. This work was partially supported by the Evans Foundation and National Science Foundation award CCF-1317694.", "abstract": "Algorithmic DNA tile systems have the potential to allow the construction by self-assembly of large structures with complex nanometer-scale details out of relatively few monomer types, but are constrained by errors in growth and the limited sequence space of orthogonal DNA sticky ends that program tile interactions. We present a tile set optimization technique that, through analysis of algorithmic growth equivalence, potentially sensitive error pathways, and potential lattice defects, can significantly reduce the size of tile systems while preserving proofreading behavior that is essential for obtaining low error rates. Applied to systems implementing multiple algorithms that are far beyond the size of currently feasible implementations, the optimization technique results in systems that are comparable in size to already-implemented experimental systems.", "date": "2018-09-07", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "37-54", "id_number": "CaltechAUTHORS:20200811-140005797", "isbn": "978-3-030-00029-5", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200811-140005797", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Evans Foundation" }, { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "contributors": { "items": [ { "id": "Doty-D", "name": { "family": "Doty", "given": "David" } }, { "id": "Dietz-H", "name": { "family": "Dietz", "given": "Hendrik" } } ] }, "doi": "10.1007/978-3-030-00030-1_3", "resource_type": "book_section", "pub_year": "2018", "author_list": "Evans, Constantine G. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/715zz-3jn69", "eprint_id": 79580, "eprint_status": "archive", "datestamp": "2023-08-19 06:53:00", "lastmod": "2023-10-20 21:49:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Srinivas-N", "name": { "family": "Srinivas", "given": "Niranjan" } }, { "id": "Parkin-J-M", "name": { "family": "Parkin", "given": "James" }, "orcid": "0000-0002-4058-2338" }, { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" } ] }, "title": "Enzyme-Free Nucleic Acid Dynamical Systems", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 American Association for the Advancement of Science. \n\nReceived 25 October 2016; accepted 25 October 2017. \n\nWe thank L. Qian for help with initial experiments and technical training; C. G. Evans for supporting the development of Piperine; A. Phillips for assistance with Visual DSD; and L. Cardelli, C. Geary, C. T. Martin, N. A. Pierce, P. W. K. Rothemund, S. L. Sparvath, B. Wolfe, F. Dannenberg, and D. Y. Zhang for helpful discussions. This work was supported by the NSF grants 0728703, 0829805, 0832824, 1317694, 1117143, and 1618895; Office of Naval Research award N00014-16-1-2139; the Gordon and Betty Moore Foundation's Programmable Molecular Technology Initiative; and National Institute of General Medical Sciences Systems Biology Center grant P50 GM081879. Data presented in the paper are archived in the Supplementary Materials.\n\nSubmitted - 138420.full.pdf
Supplemental Material - 138420-1.pdf
Supplemental Material - aal2052_Srinivas_SM.pdf
", "abstract": "An important goal of synthetic biology is to create biochemical control systems with the desired characteristics from scratch. Srinivas et al. describe the creation of a biochemical oscillator that requires no enzymes or evolved components, but rather is implemented through DNA molecules designed to function in strand displacement cascades. Furthermore, they created a compiler that could translate a formal chemical reaction network into the necessary DNA sequences that could function together to provide a specified dynamic behavior.", "date": "2017-12-15", "date_type": "published", "publication": "Science", "volume": "358", "number": "6369", "publisher": "American Association for the Advancement of Science", "pagerange": "Art. No. eaal2052", "id_number": "CaltechAUTHORS:20170731-085900027", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170731-085900027", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "NSF", "grant_number": "CCF-0829805" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CCF-1117143" }, { "agency": "NSF", "grant_number": "CCF-1618895" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-16-1-2139" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "NIH", "grant_number": "P50 GM081879" } ] }, "doi": "10.1126/science.aal2052", "primary_object": { "basename": "138420-1.pdf", "url": "https://authors.library.caltech.edu/records/715zz-3jn69/files/138420-1.pdf" }, "related_objects": [ { "basename": "138420.full.pdf", "url": "https://authors.library.caltech.edu/records/715zz-3jn69/files/138420.full.pdf" }, { "basename": "aal2052_Srinivas_SM.pdf", "url": "https://authors.library.caltech.edu/records/715zz-3jn69/files/aal2052_Srinivas_SM.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Srinivas, Niranjan; Parkin, James; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cngnd-evx96", "eprint_id": 79651, "eprint_status": "archive", "datestamp": "2023-08-19 05:08:17", "lastmod": "2023-10-26 17:00:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Thubagere-A-J", "name": { "family": "Thubagere", "given": "Anupama J." } }, { "id": "Li-Wei", "name": { "family": "Li", "given": "Wei" }, "orcid": "0000-0003-2543-2558" }, { "id": "Johnson-R-F", "name": { "family": "Johnson", "given": "Robert F." } }, { "id": "Chen-Zibo", "name": { "family": "Chen", "given": "Zibo" }, "orcid": "0000-0003-2990-2895" }, { "id": "Doroudi-S", "name": { "family": "Doroudi", "given": "Shayan" } }, { "id": "Lee-Yae-Lim", "name": { "family": "Lee", "given": "Yae Lim" } }, { "id": "Izatt-G", "name": { "family": "Izatt", "given": "Gregory" } }, { "id": "Wittman-S", "name": { "family": "Wittman", "given": "Sarah" } }, { "id": "Srinivas-N", "name": { "family": "Srinivas", "given": "Niranjan" } }, { "id": "Woods-D", "name": { "family": "Woods", "given": "Damien" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" } ] }, "title": "A cargo-sorting DNA robot", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 American Association for the Advancement of Science. \n\nWe thank R. Murray, P. Rothemund, C. Thachuk, P. Yin, and R. Jungmann for discussions and suggestions. Z.C., S.D., Y.L.L., G.I., and S.W. were supported by Caltech Summer Undergraduate Research Fellowships. N.S., D.W., and E.W. were supported by an NSF Expedition in Computing (0832824). A.J.T. was supported by an NSF grant (1351081). W.L. was supported by an NSF Expedition in Computing (1317694). R.F.J. was supported by an NSF Graduate Research Fellowship. L.Q. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (1010684) and a Faculty Early Career Development Award from the NSF (1351081). All data are reported in the main text and the supplementary materials.\n\nSupplemental Material - aan6558_Thubagere_SM.pdf
", "abstract": "Single-stranded DNA robots can move over the surface of a DNA origami sheet and sort molecular cargoes. Thubagere et al. developed a simple algorithm for recognizing two types of molecular cargoes and their drop-off destinations on the surface (see the Perspective by Reif). The DNA robot, which has three modular functional domains, repeatedly picks up the two types of molecules and then places them at their target destinations. No additional power is required because the DNA robot does this by random walking across the origami surface.", "date": "2017-09-15", "date_type": "published", "publication": "Science", "volume": "357", "number": "6356", "publisher": "American Association for the Advancement of Science", "pagerange": "Art. No. eaan6558", "id_number": "CaltechAUTHORS:20170731-174213645", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170731-174213645", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1351081" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Burroughs Wellcome Fund", "grant_number": "1010684" } ] }, "doi": "10.1126/science.aan6558", "primary_object": { "basename": "aan6558_Thubagere_SM.pdf", "url": "https://authors.library.caltech.edu/records/cngnd-evx96/files/aan6558_Thubagere_SM.pdf" }, "resource_type": "article", "pub_year": "2017", "author_list": "Thubagere, Anupama J.; Li, Wei; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1pfn7-t7n80", "eprint_id": 91151, "eprint_status": "archive", "datestamp": "2023-08-19 04:45:15", "lastmod": "2024-01-14 21:13:24", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Badelt-S", "name": { "family": "Badelt", "given": "Stefan" } }, { "id": "Shin-Seung-Woo", "name": { "family": "Shin", "given": "Seung Woo" } }, { "id": "Johnson-R-F", "name": { "family": "Johnson", "given": "Robert F." } }, { "id": "Dong-Qing", "name": { "family": "Dong", "given": "Qing" } }, { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "A General-Purpose CRN-to-DSD Compiler with Formal Verification, Optimization, and Simulation Capabilities", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 Springer International Publishing AG 2017. \n\nFirst Online: 24 August 2017. \n\nWe thank the U.S. National Science Foundation for support:\nNSF Grant CCF-1213127 and NSF Grant CCF-1317694 (\"The Molecular Programming Project\"). The Gordon and Betty Moore Foundation's Programmable Molecular Technology Initiative (PMTI). SB is funded by the Caltech Biology and Biological Engineering Division Fellowship.", "abstract": "The mathematical formalism of mass-action chemical reaction networks (CRNs) has been proposed as a mid-level programming language for dynamic molecular systems. Several systematic methods for translating CRNs into domain-level strand displacement (DSD) systems have been developed theoretically, and in some cases demonstrated experimentally. Software that facilitates the simulation of CRNs and DSDs, and that helps automate the construction of DSDs from CRNs, has been instrumental in advancing the field, but as yet has not incorporated the fundamental enabling concept for programming languages and compilers: a rigorous abstraction hierarchy with well-defined semantics at each level, and rigorous correctness proofs establishing the correctness of compilation from a higher level to a lower level. Here, we present a CRN-to-DSD compiler, Nuskell, that makes a first step in this direction. To support the wide range of translation schemes that have already been proposed in the literature, as well as potential new ones that are yet to be proposed, Nuskell provides a domain-specific programming language for translation schemes. A notion of correctness is established on a case-by-case basis using the rate-independent stochastic-level theories of pathway decomposition equivalence and/or CRN bisimulation. The \"best\" DSD implementation for a given CRN can be found by comparing the molecule size, network size, or simulation behavior for a variety of translation schemes. These features are illustrated with a 3-reaction oscillator CRN and a 32-reaction feedforward boolean circuit CRN.", "date": "2017-08-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "232-248", "id_number": "CaltechAUTHORS:20181126-085056720", "isbn": "978-3-319-66798-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-085056720", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Division of Biology and Biological Engineering" } ] }, "contributors": { "items": [ { "id": "Brijder-R", "name": { "family": "Brijder", "given": "Robert" } }, { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" } } ] }, "doi": "10.1007/978-3-319-66799-7_15", "resource_type": "book_section", "pub_year": "2017", "author_list": "Badelt, Stefan; Shin, Seung Woo; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tgwe9-zwv34", "eprint_id": 91153, "eprint_status": "archive", "datestamp": "2023-08-21 21:37:24", "lastmod": "2024-01-14 21:13:26", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Poole-W", "name": { "family": "Poole", "given": "William" } }, { "id": "Ortiz-Mu\u00f1oz-A", "name": { "family": "Ortiz-Mu\u00f1oz", "given": "Andr\u00e9s" }, "orcid": "0000-0003-1824-3230" }, { "id": "Behera-A", "name": { "family": "Behera", "given": "Abhishek" } }, { "id": "Jones-N-S", "name": { "family": "Jones", "given": "Nick S." } }, { "id": "Ouldridge-T-E", "name": { "family": "Ouldridge", "given": "Thomas E." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Gopalkrishnan-M", "name": { "family": "Gopalkrishnan", "given": "Manoj" } } ] }, "title": "Chemical Boltzmann Machines", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "DNA origami; Knot theory; Graph theory; Chinese postman problem", "note": "\u00a9 Springer International Publishing AG 2017. \n\nFirst Online: 24 August 2017. \n\nThis work was supported in part by U.S. National Science\nFoundation (NSF) graduate fellowships to WP and to AOM, by NSF grant CCF-1317694 to EW, and by the Gordon and Betty Moore Foundation through Grant GBMF2809 to the Caltech Programmable Molecular Technology Initiative (PMTI), by a Royal Society University Research Fellowship to TEO, and by a Bharti Centre for Communication in IIT Bombay award to AB.", "abstract": "How smart can a micron-sized bag of chemicals be? How can an artificial or real cell make inferences about its environment? From which kinds of probability distributions can chemical reaction networks sample? We begin tackling these questions by showing three ways in which a stochastic chemical reaction network can implement a Boltzmann machine, a stochastic neural network model that can generate a wide range of probability distributions and compute conditional probabilities. The resulting models, and the associated theorems, provide a road map for constructing chemical reaction networks that exploit their native stochasticity as a computational resource. Finally, to show the potential of our models, we simulate a chemical Boltzmann machine to classify and generate MNIST digits in-silico.", "date": "2017-08-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "210-231", "id_number": "CaltechAUTHORS:20181126-090207704", "isbn": "978-3-319-66798-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-090207704", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "Royal Society" }, { "agency": "India Institute of Technology" } ] }, "contributors": { "items": [ { "id": "Brijder-R", "name": { "family": "Brijder", "given": "Robert" } }, { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" } } ] }, "doi": "10.1007/978-3-319-66799-7_14", "resource_type": "book_section", "pub_year": "2017", "author_list": "Poole, William; Ortiz-Mu\u00f1oz, Andr\u00e9s; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xp5nf-fxf94", "eprint_id": 91155, "eprint_status": "archive", "datestamp": "2023-08-19 04:45:31", "lastmod": "2024-01-14 21:13:30", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zolaktaf-S", "name": { "family": "Zolaktaf", "given": "Sedigheh" } }, { "id": "Dannenberg-F", "name": { "family": "Dannenberg", "given": "Frits" } }, { "id": "Rudelis-X", "name": { "family": "Rudelis", "given": "Xander" } }, { "id": "Condon-A", "name": { "family": "Condon", "given": "Anne" } }, { "id": "Schaeffer-J-M", "name": { "family": "Schaeffer", "given": "Joseph M." } }, { "id": "Schmidt-Mark", "name": { "family": "Schmidt", "given": "Mark" } }, { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Inferring Parameters for an Elementary Step Model of DNA Structure Kinetics with Locally Context-Dependent Arrhenius Rates", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 Springer International Publishing AG 2017. \n\nFirst Online: 24 August 2017. \n\nWe thank the U.S. National Science Foundation (awards 0832824, 1213127, 1317694, 1643606), the Gordon and Betty Moore Foundation's Programmable Molecular Technology Initiative, and the Natural Sciences and Engineering Research Council of Canada for support. We also thank the anonymous reviewers for their helpful comments and suggestions.", "abstract": "Models of nucleic acid thermal stability are calibrated to a wide range of experimental observations, and typically predict equilibrium probabilities of nucleic acid secondary structures with reasonable accuracy. By comparison, a similar calibration and evaluation of nucleic acid kinetic models to a broad range of measurements has not been attempted so far. We introduce an Arrhenius model of interacting nucleic acid kinetics that relates the activation energy of a state transition with the immediate local environment of the affected base pair. Our model can be used in stochastic simulations to estimate kinetic properties and is consistent with existing thermodynamic models. We infer parameters for our model using an ensemble Markov chain Monte Carlo (MCMC) approach on a training dataset with 320 kinetic measurements of hairpin closing and opening, helix association and dissociation, bubble closing and toehold-mediated strand exchange. Our new model surpasses the performance of the previously established Metropolis model both on the training set and on a testing set of size 56 composed of toehold-mediated 3-way strand displacement with mismatches and hairpin opening and closing rates: reaction rates are predicted to within a factor of three for 93.4% and 78.5% of reactions for the training and testing sets, respectively.", "date": "2017-08-24", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "172-187", "id_number": "CaltechAUTHORS:20181126-091545698", "isbn": "978-3-319-66798-0", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181126-091545698", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "IIS-1213127" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "CHE-1643606" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" } ] }, "contributors": { "items": [ { "id": "Brijder-R", "name": { "family": "Brijder", "given": "Robert" } }, { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" } } ] }, "doi": "10.1007/978-3-319-66799-7_12", "resource_type": "book_section", "pub_year": "2017", "author_list": "Zolaktaf, Sedigheh; Dannenberg, Frits; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ms029-b9h13", "eprint_id": 77444, "eprint_status": "archive", "datestamp": "2023-08-19 03:42:47", "lastmod": "2023-10-25 23:03:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Evans-C-G", "name": { "family": "Evans", "given": "Constantine G." }, "orcid": "0000-0002-7053-1670" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Physical principles for DNA tile self-assembly", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2017 The Royal Society of Chemistry. \n\nReceived 15th October 2016; First published on 10th May 2017. \n\nThis work was partially supported by National Science Foundation awards 0832824, 1162589, and 1317694.", "abstract": "DNA tiles provide a promising technique for assembling structures with nanoscale resolution through self-assembly by basic interactions rather than top-down assembly of individual structures. Tile systems can be programmed to grow based on logical rules, allowing for a small number of tile types to assemble large, complex assemblies that can retain nanoscale resolution. Such algorithmic systems can even assemble different structures using the same tiles, based on inputs that seed the growth. While programming and theoretical analysis of tile self-assembly often makes use of abstract logical models of growth, experimentally implemented systems are governed by nanoscale physical processes that can lead to very different behavior, more accurately modeled by taking into account the thermodynamics and kinetics of tile attachment and detachment in solution. This review discusses the relationships between more abstract and more physically realistic tile assembly models. A central concern is how consideration of model differences enables the design of tile systems that robustly exhibit the desired abstract behavior in realistic physical models and in experimental implementations. Conversely, we identify situations where self-assembly in abstract models can not be well-approximated by physically realistic models, putting constraints on physical relevance of the abstract models. To facilitate the discussion, we introduce a unified model of tile self-assembly that clarifies the relationships between several well-studied models in the literature. Throughout, we highlight open questions regarding the physical principles for DNA tile self-assembly.", "date": "2017-06-21", "date_type": "published", "publication": "Chemical Society Reviews", "volume": "46", "number": "12", "publisher": "Royal Society of Chemistry", "pagerange": "3808-3829", "id_number": "CaltechAUTHORS:20170515-101843093", "issn": "0306-0012", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170515-101843093", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1162589" }, { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "doi": "10.1039/c6cs00745g", "resource_type": "article", "pub_year": "2017", "author_list": "Evans, Constantine G. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sm0c6-t7n21", "eprint_id": 79158, "eprint_status": "archive", "datestamp": "2023-08-20 13:23:50", "lastmod": "2024-01-13 20:35:50", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schiefer-N", "name": { "family": "Schiefer", "given": "Nicholas" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Time Complexity of Computation and Construction in the Chemical Reaction Network-Controlled Tile Assembly Model", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2016 Springer International Publishing Switzerland. \n\nFirst Online: 14 August 2016.\n\nWe acknowledge financial support from National Science Foundation grant CCF-1317694 and the Soli Deo Gloria Summer Undergraduate Research Fellowship at the California Institute of Technology. We also thank Dave Doty and Damien Woods for their insights.", "abstract": "In isolation, chemical reaction networks and tile-based self-assembly are well-studied models of chemical computation. Previously, we introduced the chemical reaction network-controlled tile assembly model (CRN-TAM), in which a stochastic chemical reaction network can act as a non-local control and signalling system for tile-based assembly, and showed that the CRN-TAM can perform several tasks related to the simulation of Turing machines and construction of algorithmic shapes with lower space or program complexity than in either of its parent models. Here, we introduce a kinetic variant of the CRN-TAM and investigate the time complexity of computation and construction. We analyze the time complexity of decision problems in the CRN-TAM, and show that decidable languages can be decided as efficiently by CRN-TAM programs as by Turing machines. We also give a lower bound for the space-time complexity of CRN-TAM computation that rules out efficient parallel stack machines. We provide efficient parallel implementations of non-deterministic computations, showing among other things that CRN-TAM programs can decide languages in NTIME(f(n))\u2229coNTIME(f(n)) in O(f(n)+n+logc) time with 1\u2212exp(\u2212c) probability, using volume exponential in n. Lastly, we provide basic mechanisms for parallel computations that share information and illustrate the limits of parallel computation in the CRN-TAM.", "date": "2016-08-14", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "165-182", "id_number": "CaltechAUTHORS:20170718-122926337", "isbn": "978-3-319-43993-8", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170718-122926337", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" } ] }, "contributors": { "items": [ { "id": "Rondelez-Y", "name": { "family": "Rondelez", "given": "Yannick" } }, { "id": "Woods-D", "name": { "family": "Woods", "given": "Damien" } } ] }, "doi": "10.1007/978-3-319-43994-5_11", "resource_type": "book_section", "pub_year": "2016", "author_list": "Schiefer, Nicholas and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5a09z-v9n43", "eprint_id": 99129, "eprint_status": "archive", "datestamp": "2023-08-20 13:23:53", "lastmod": "2024-01-14 21:58:58", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnson-R-F", "name": { "family": "Johnson", "given": "Robert F." } }, { "id": "Dong-Qing", "name": { "family": "Dong", "given": "Qing" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Verifying Chemical Reaction Network Implementations: A Bisimulation Approach", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2016 Springer International Publishing Switzerland. \n\nFirst Online 14 August 2016. \n\nThe authors would like to thank Chris Thachuk, Damien Woods, Dave Doty, and Seung Woo Shin for helpful discussions. RFJ and EW were supported by NSF grants 1317694, 1213127, and 0832824. RFJ was supported by Caltech's Summer Undergraduate Research Fellowship program and an NSF graduate fellowship. QD's current affiliation is Epic Systems, Madison, Wisconsin.", "abstract": "Efforts in programming DNA and other biological molecules have recently focused on general schemes to physically implement arbitrary Chemical Reaction Networks. Errors in some of the proposed schemes have driven a desire for formal verification methods. We show that by interpreting each implementation species as a set of formal species, the concept of weak bisimulation can be adapted to CRNs in a way that agrees with an intuitive notion of a correct implementation. We give examples of how to use bisimulation to prove the correctness of an implementation or detect subtle problems. We examine the complexity of finding a valid interpretation between two CRNs if one exists, and that of checking whether an interpretation is valid. We show that both are PSPACE-complete in the general case, but are NP-complete and polynomial-time respectively under an assumption that holds in many practical cases. We give algorithms for both of those problems.", "date": "2016-08-14", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "114-134", "id_number": "CaltechAUTHORS:20191007-155606936", "isbn": "9783319439938", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191007-155606936", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NSF", "grant_number": "IIS-1213127" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "contributors": { "items": [ { "id": "Rondelez-Y", "name": { "family": "Rondelez", "given": "Yannick" } }, { "id": "Woods-D", "name": { "family": "Woods", "given": "Damien" } } ] }, "doi": "10.1007/978-3-319-43994-5_8", "resource_type": "book_section", "pub_year": "2016", "author_list": "Johnson, Robert F.; Dong, Qing; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zg79y-rzy97", "eprint_id": 61731, "eprint_status": "archive", "datestamp": "2023-08-22 16:49:58", "lastmod": "2023-10-25 15:41:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hariadi-Rizal-F", "name": { "family": "Hariadi", "given": "Rizal F." }, "orcid": "0000-0001-7840-859X" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Yurke-Bernard", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" } ] }, "title": "Determining hydrodynamic forces in bursting bubbles using DNA nanotube mechanics", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA nanotechnology; polymer dynamics; hydrodynamics", "note": "\u00a9 2015 National Academy of Sciences. Freely available online through the PNAS open access option. \n\nEdited by Eric D. Siggia, The Rockefeller University, New York, NY, and approved September 4, 2015 (received for review December 24, 2014). Published online before print October 26, 2015. \n\nThe authors gratefully acknowledge Rebecca Schulman, Damien Woods, Paul Rothemund, Carter Swanson, Manu Prakash, John O. Dabiri, and Sandra Troian for helpful discussions. This work was supported by the National Science Foundation through Grants EMT-0622254, NIRT-0608889, CCF-0832824 (The Molecular Programming Project), and CCF-0855212. \n\nAuthor contributions: R.F.H., E.W., and B.Y. designed research; R.F.H. and B.Y. performed research; R.F.H., E.W., and B.Y. contributed new reagents/analytic tools; R.F.H., E.W., and B.Y. analyzed data; and R.F.H., E.W., and B.Y. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nThis article is a PNAS Direct Submission. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1424673112/-/DCSupplemental.\n\nPublished - PNAS-2015-Hariadi-E6086-95.pdf
Supplemental Material - pnas.1424673112.sapp.pdf
Supplemental Material - pnas.1424673112.sm01.mov
Supplemental Material - pnas.201424673SI.pdf
", "abstract": "Quantifying the mechanical forces produced by fluid flows within the ocean is critical to understanding the ocean's environmental phenomena. Such forces may have been instrumental in the origin of life by driving a primitive form of self-replication through fragmentation. Among the intense sources of hydrodynamic shear encountered in the ocean are breaking waves and the bursting bubbles produced by such waves. On a microscopic scale, one expects the surface-tension\u2013driven flows produced during bubble rupture to exhibit particularly high velocity gradients due to the small size scales and masses involved. However, little work has examined the strength of shear flow rates in commonly encountered ocean conditions. By using DNA nanotubes as a novel fluid flow sensor, we investigate the elongational rates generated in bursting films within aqueous bubble foams using both laboratory buffer and ocean water. To characterize the elongational rate distribution associated with a bursting bubble, we introduce the concept of a fragmentation volume and measure its form as a function of elongational flow rate. We find that substantial volumes experience surprisingly large flow rates: during the bursting of a bubble having an air volume of 10 mm^3, elongational rates at least as large as \u03f5 = 1.0\u00d710^8 s^(\u22121) are generated in a fragmentation volume of \u223c2\u00d710^(\u22126) \u03bcL. The determination of the elongational strain rate distribution is essential for assessing how effectively fluid motion within bursting bubbles at the ocean surface can shear microscopic particles and microorganisms, and could have driven the self-replication of a protobiont.", "date": "2015-11-10", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "112", "number": "45", "publisher": "National Academy of Sciences", "pagerange": "E6086-E6095", "id_number": "CaltechAUTHORS:20151030-075058188", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151030-075058188", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0622254" }, { "agency": "NSF", "grant_number": "CBET-0608889" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-0855212" } ] }, "doi": "10.1073/pnas.1424673112", "pmcid": "PMC4653207", "primary_object": { "basename": "PNAS-2015-Hariadi-E6086-95.pdf", "url": "https://authors.library.caltech.edu/records/zg79y-rzy97/files/PNAS-2015-Hariadi-E6086-95.pdf" }, "related_objects": [ { "basename": "pnas.1424673112.sapp.pdf", "url": "https://authors.library.caltech.edu/records/zg79y-rzy97/files/pnas.1424673112.sapp.pdf" }, { "basename": "pnas.1424673112.sm01.mov", "url": "https://authors.library.caltech.edu/records/zg79y-rzy97/files/pnas.1424673112.sm01.mov" }, { "basename": "pnas.201424673SI.pdf", "url": "https://authors.library.caltech.edu/records/zg79y-rzy97/files/pnas.201424673SI.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Hariadi, Rizal F.; Winfree, Erik; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b9keh-ytk18", "eprint_id": 104932, "eprint_status": "archive", "datestamp": "2023-08-22 16:01:35", "lastmod": "2024-01-15 17:04:14", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" } ] }, "title": "Leakless DNA Strand Displacement Systems", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Strand Displacement; Leak Pathway; Bottom Strand; Complementary Domain; Hypothetical Experiment", "note": "\u00a9 2015 Springer International Publishing Switzerland. \n\nFirst Online: 21 July 2015. \n\nThe authors are supported by a Banting Fellowship (CT), NSF CCF/HCC Grant No. 1213127, NSF CCF Grant No. 1317694, and NIGMS Systems Biology Center grant P50 GM081879 (DS). We thank Boya Wang and Robert Machinek for helpful discussions.", "abstract": "While current experimental demonstrations have been limited to small computational tasks, DNA strand displacement systems (DSD systems) [25] hold promise for sophisticated information processing within chemical or biological environments. A DSD system encodes designed reactions that are facilitated by three-way or four-way toehold-mediated strand displacement. However, such systems are capable of spurious displacement events that lead to leak: incorrect signal production. We have identified sources of leak pathways in typical existing DSD schemes that rely on toehold sequestration and are susceptible to toeless strand displacement (i.e. displacement reactions that occur despite the absence of a toehold). Based on this understanding, we propose a simple, domain-level motif for the design of leak-resistant DSD systems. This motif forms the basis of a number of DSD schemes that do not rely on toehold sequestration alone to prevent spurious displacements. Spurious displacements are still possible in our systems, but require multiple, low probability events to occur. Our schemes can implement combinatorial Boolean logic formulas and can be extended to implement arbitrary chemical reaction networks.", "date": "2015-07-21", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "133-153", "id_number": "CaltechAUTHORS:20200812-120743269", "isbn": "978-3-319-21998-1", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200812-120743269", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "NIH", "grant_number": "P50 GM081879" } ] }, "contributors": { "items": [ { "id": "Phillips-A", "name": { "family": "Phillips", "given": "Andrew" } }, { "id": "Yin-Peng", "name": { "family": "Yin", "given": "Peng" } } ] }, "doi": "10.1007/978-3-319-21999-8_9", "resource_type": "book_section", "pub_year": "2015", "author_list": "Thachuk, Chris; Winfree, Erik; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pvacj-t2m32", "eprint_id": 104920, "eprint_status": "archive", "datestamp": "2023-08-22 16:01:28", "lastmod": "2024-01-15 17:04:10", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schaeffer-Joseph-Malcolm", "name": { "family": "Schaeffer", "given": "Joseph Malcolm" } }, { "id": "Thachuk-C", "name": { "family": "Thachuk", "given": "Chris" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Stochastic Simulation of the Kinetics of Multiple Interacting Nucleic Acid Strands", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Single Base Pair; Continuous Time Markov Process; Gillespie Algorithm; Loop Graph; Pseudoknotted Structure", "note": "\u00a9 2015 Springer International Publishing Switzerland. \n\nFirst Online: 21 July 2015. \n\nWe are greatly indebted to years of insights, suggestions, and feedback from Niles Pierce, Robert Dirks, Justin Bois, and Victor Beck, especially their contributions to the formulation of the energy model and the first step simulation mode. This work has been funded by National Science Foundation grants DMS-0506468, CCF-0832824, CCF-1213127, CCF-1317694, and the Gordon and Betty Moore Foundation through the Caltech Programmable Molecular Technology Initiative.", "abstract": "DNA nanotechnology is an emerging field which utilizes the unique structural properties of nucleic acids in order to build nanoscale devices, such as logic gates, motors, walkers, and algorithmic structures. Predicting the structure and interactions of a DNA device requires effective modeling of both the thermodynamics and the kinetics of the DNA strands within the system. The kinetics of a set of DNA strands can be modeled as a continuous time Markov process through the state space of all secondary structures. The primary means of exploring the kinetics of a DNA system is by simulating trajectories through the state space and aggregating data over many such trajectories. We expand on previous work by extending the thermodynamics and kinetics models to handle multiple strands in a fixed volume, in a way that is consistent with previous models. We developed data structures and algorithms that allow us to take advantage of local properties of secondary structure, improving the efficiency of the simulator so that we can handle reasonably large systems. Finally, we illustrate the simulator's analysis methods on a simple case study.", "date": "2015-07-21", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham", "pagerange": "194-211", "id_number": "CaltechAUTHORS:20200811-152309514", "isbn": "978-3-319-21998-1", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200811-152309514", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMS-0506468" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1213127" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Programmable Molecular Technology Initiative" } ] }, "contributors": { "items": [ { "id": "Phillips-Andrew", "name": { "family": "Phillips", "given": "Andrew" } }, { "id": "Yin-Peng", "name": { "family": "Yin", "given": "Peng" } } ] }, "doi": "10.1007/978-3-319-21999-8_13", "resource_type": "book_section", "pub_year": "2015", "author_list": "Schaeffer, Joseph Malcolm; Thachuk, Chris; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qmv18-wee30", "eprint_id": 57585, "eprint_status": "archive", "datestamp": "2023-08-22 15:37:54", "lastmod": "2023-10-23 17:33:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Wright-Christina", "name": { "family": "Wright", "given": "Christina" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Increasing Redundancy Exponentially Reduces Error Rates during Algorithmic Self-Assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA nanotechnology; algorithmic self-assembly; error correction; crystal growth", "note": "\u00a9 2015 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived for review December 31, 2014 and accepted April 29, 2015. Publication Date (Web): May 12, 2015. \n\nThe authors wish to thank Paul Rothemund, Robert Barish and Ho-Lin Chen for valuable advice and discussion. This work was supported by NSF Grants CCF-0432193, CCF-0523761, and CCF-0832824 (The Molecular Programming Project), NASA Astrobiology NNG06GA50G, FENA Theme 2, a Caltech SURF award and the Miller Institute for Basic Science.\n\nPublished - nn507493s.pdf
Supplemental Material - nn507493s_si_001.pdf
", "abstract": "While biology demonstrates that molecules can reliably transfer information and compute, design principles for implementing complex molecular computations in vitro are still being developed. In electronic computers, large-scale computation is made possible by redundancy, which allows errors to be detected and corrected. Increasing the amount of redundancy can exponentially reduce errors. Here, we use algorithmic self-assembly, a generalization of crystal growth in which the self-assembly process executes a program for growing an object, to examine experimentally whether redundancy can analogously reduce the rate at which errors occur during molecular self-assembly. We designed DNA double-crossover molecules to algorithmically self-assemble ribbon crystals that repeatedly copy a short bitstring, and we measured the error rate when each bit is encoded by 1 molecule, or redundantly encoded by 2, 3, or 4 molecules. Under our experimental conditions, each additional level of redundancy decreases the bitwise error rate by a factor of roughly 3, with the 4-redundant encoding yielding an error rate less than 0.1%. While theory and simulation predict that larger improvements in error rates are possible, our results already suggest that by using sufficient redundancy it may be possible to algorithmically self-assemble micrometer-sized objects with programmable, nanometer-scale features.", "date": "2015-06", "date_type": "published", "publication": "ACS Nano", "volume": "9", "number": "6", "publisher": "American Chemical Society", "pagerange": "5760-5771", "id_number": "CaltechAUTHORS:20150518-090813566", "issn": "1936-0851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150518-090813566", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0432193" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NASA", "grant_number": "NNG06GA50G" }, { "agency": "Functional Engineered Nano Architectonics (FENA)" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "Miller Institute for Basic Research in Science" } ] }, "doi": "10.1021/nn507493s", "primary_object": { "basename": "nn507493s.pdf", "url": "https://authors.library.caltech.edu/records/qmv18-wee30/files/nn507493s.pdf" }, "related_objects": [ { "basename": "nn507493s_si_001.pdf", "url": "https://authors.library.caltech.edu/records/qmv18-wee30/files/nn507493s_si_001.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Schulman, Rebecca; Wright, Christina; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zfjk8-bpp45", "eprint_id": 55418, "eprint_status": "archive", "datestamp": "2023-08-20 05:34:55", "lastmod": "2023-10-20 22:13:28", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hariadi-R-F", "name": { "family": "Hariadi", "given": "Rizal F." } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Thermodynamics and kinetics of DNA nanotube polymerization from single-filament measurements", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 04 Dec 2013; accepted 20 Jan 2015; first published online 20 Feb 2015. \n\nWe would like to acknowledge Rebecca Schulman, Damien Woods, Matthew Cook, Tosan Omabegho, Heun Jin Lee, Ethan Garner, Michael Diehl, Zahid Yaqoob, Nadine Dabby, and Paul Rothemund for their helpful discussions. The authors especially thank Rebecca Schulman and Ann McEvoy for pointing our attention to glass capillary chambers, and Matthew Cook for analysis of 2D crystal growth front dynamics. The length measurements were made possible\nbecause of Jeffry Kuhn's generosity in sharing his filament snapping and length measurement codes. This work was supported by NSF through the grants EMT-0622254, NIRT-0608889, CCF-0832824 (The Molecular Programming Project), and CCF-0855212.\n\nPublished - c3sc53331j.pdf
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", "abstract": "DNA nanotubes provide a programmable architecture for molecular self-assembly and can serve as model systems for one-dimensional biomolecular assemblies. While a variety of DNA nanotubes have been synthesized and employed as models for natural biopolymers, an extensive investigation of DNA nanotube kinetics and thermodynamics has been lacking. Using total internal reflection microscopy, DNA nanotube polymerization was monitored in real time at the single filament level over a wide range of free monomer concentrations and temperatures. The measured polymerization rates were subjected to a global nonlinear fit based on polymerization theory in order to simultaneously extract kinetic and thermodynamic parameters. For the DNA nanotubes used in this study, the association rate constant is (5.99 \u00b1 0.15) \u00d7 10^5 M^(\u22121) s^(\u22121), the enthalpy is 87.9 \u00b1 2.0 kcal mol^(\u22121), and the entropy is 0.252 \u00b1 0.006 kcal mol^(\u22121) K^(\u22121). The qualitative and quantitative similarities between the kinetics of DNA nanotubes, actin filaments, and microtubules polymerization highlight the prospect of building complex dynamic systems from DNA molecules inspired by biological architecture.", "date": "2015-04", "date_type": "published", "publication": "Chemical Science", "volume": "6", "number": "4", "publisher": "Royal Society of Chemistry", "pagerange": "2252-2267", "id_number": "CaltechAUTHORS:20150302-131739870", "issn": "2041-6520", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150302-131739870", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "EMT-0622254" }, { "agency": "NSF", "grant_number": "NIRT-0608889" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-0855212" } ] }, "doi": "10.1039/c3sc53331j", "pmcid": "PMC5645730", "primary_object": { "basename": "c3sc53331j.pdf", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j.pdf" }, "related_objects": [ { "basename": "c3sc53331j1.pdf", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j1.pdf" }, { "basename": "c3sc53331j2.mov", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j2.mov" }, { "basename": "c3sc53331j3.mov", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j3.mov" }, { "basename": "c3sc53331j4.mov", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j4.mov" }, { "basename": "c3sc53331j5.mov", "url": "https://authors.library.caltech.edu/records/zfjk8-bpp45/files/c3sc53331j5.mov" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Hariadi, Rizal F.; Yurke, Bernard; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0tq84-hgv56", "eprint_id": 60077, "eprint_status": "archive", "datestamp": "2023-08-20 04:10:26", "lastmod": "2024-01-13 16:24:42", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schiefer-N", "name": { "family": "Schiefer", "given": "Nicholas" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Universal Computation and Optimal Construction in the Chemical Reaction Network-Controlled Tile Assembly Model", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2015 Springer. \n\nWe acknowledge financial support from National Science Foundation grant CCF-1317694. We also thank Dave Doty, for his helpful comments and suggestions, and Kevin Li, for his useful suggestions on an early draft of this paper.", "abstract": "Tile-based self-assembly and chemical reaction networks provide two well-studied models of scalable DNA-based computation. Although tile self-assembly provides a powerful framework for describing Turing-universal self-assembling systems, assembly logic in tile self-assembly is localized, so that only the nearby environment can affect the process of self-assembly. We introduce a new model of tile-based self-assembly in which a well-mixed chemical reaction network interacts with self-assembling tiles to exert non-local control on the self-assembly process. Through simulation of multi-stack machines, we demonstrate that this new model is efficiently Turing-universal, even when restricted to unbounded space in only one spatial dimension. Using a natural notion of program complexity, we also show that this new model can produce many complex shapes with programs of lower complexity. Most notably, we show that arbitrary connected shapes can be produced by a program with complexity bounded by the Kolmogorov complexity of the shape, without the large scale factor that is required for the analogous result in the abstract tile assembly model. These results suggest that controlled self-assembly provides additional algorithmic power over tile-only self-assembly, and that non-local control enhances our ability to perform computation and algorithmically self-assemble structures from small input programs.", "date": "2015", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "34-54", "id_number": "CaltechAUTHORS:20150904-111819530", "isbn": "978-3-319-21998-1", "book_title": "DNA Computing and Molecular Programming: 21st International Conference, DNA 21, Boston and Cambridge, MA, USA, August 17-21, 2015. Proceedings", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150904-111819530", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1317694" } ] }, "doi": "10.1007/978-3-319-21999-8_3", "resource_type": "book_section", "pub_year": "2015", "author_list": "Schiefer, Nicholas and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zneh1-k5y76", "eprint_id": 79192, "eprint_status": "archive", "datestamp": "2023-08-20 02:48:39", "lastmod": "2024-01-13 20:35:57", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Parallel and Scalable Computation and Spatial Dynamics with DNA-Based Chemical Reaction Networks on a Surface", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2014 Springer International Publishing Switzerland. \n\nWe thank Ho-Lin Chen and David Yu Zhang for insightful\ndiscussions and suggestions. LQ and EW were supported by the Molecular Programming Project under NSF expedition in computing (0832824 and 1317694). LQ was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (1010684), a Faculty Early Career Development Award from NSF (1351081), and a Okawa Foundation Research Grant (0656180).", "abstract": "We propose a theoretical framework that uses a novel DNA strand displacement mechanism to implement abstract chemical reaction networks (CRNs) on the surface of a DNA nanostructure, and show that surface CRNs can perform efficient algorithmic computation and create complex spatial dynamics. We argue that programming molecular behaviors with surface CRNs is systematic, parallel and scalable.", "date": "2014-09", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "114-131", "id_number": "CaltechAUTHORS:20170719-084200345", "isbn": "978-3-319-11294-7", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170719-084200345", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Burroughs Wellcome Fund", "grant_number": "1010684" }, { "agency": "NSF", "grant_number": "CCF-1351081" }, { "agency": "Okawa Foundation", "grant_number": "0656180" } ] }, "contributors": { "items": [ { "id": "Murata-Satoshi", "name": { "family": "Murata", "given": "Satoshi" } }, { "id": "Kobayashi-Satoshi", "name": { "family": "Kobayashi", "given": "Satoshi" } } ] }, "doi": "10.1007/978-3-319-11295-4_8", "resource_type": "book_section", "pub_year": "2014", "author_list": "Qian, Lulu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fhx14-66450", "eprint_id": 45185, "eprint_status": "archive", "datestamp": "2023-08-20 00:07:38", "lastmod": "2023-10-20 22:58:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Weitz-Maximilian", "name": { "family": "Weitz", "given": "Maximilian" } }, { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Kapsner-Korbinian", "name": { "family": "Kapsner", "given": "Korbinian" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Franco-Elisa", "name": { "family": "Franco", "given": "Elisa" } }, { "id": "Simmel-F-C", "name": { "family": "Simmel", "given": "Friedrich C." }, "orcid": "0000-0003-3829-3446" } ] }, "title": "Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Macmillan Publishers Limited.\nReceived 24 October 2012; Accepted 13 January 2014; Published online 16 February 2014; Corrected online 22 April 2014.\n\nThe authors acknowledge financial support by the National Science Foundation grants CCF-0832824 (The Molecular Programming Project) and CMMI-1266402, by the Bourns\nCollege of Engineering at the University of California at Riverside (UC), the UC Regents Faculty Development Fellowship, the European Commission FP7 grant no. 248919\n(Bacterial Computing with Engineered Populations), the German Research Foundation Cluster of Excellence Nanosystems Initiative Munich and the Elite Network of Bayern. Surfactant E2K0660 was supplied by RainDance Technologies. We acknowledge E. Friedrichs and R. Jungmann for initial experiments; U. Gerland, R. Murray and\nN. Karlsson for useful discussions, advice and support; and C. Martin, L. Ram\u00ecrez-Tapia, E. Stahl and H. Dietz for providing fluorescently labelled T7 RNAP.\n\nAuthor contributions:\nE.W., E.F. and F.C.S. designed the research; M.W., J.K. and E.F. performed the research;\nM.W., J.K., K.K. and E.F. analysed the data; E.W., E.F. and F.C.S wrote the paper.\n\nSupplemental Material - nchem.1869-s1.pdf
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", "abstract": "In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function", "date": "2014-04", "date_type": "published", "publication": "Nature Chemistry", "volume": "6", "number": "4", "publisher": "Nature Publishing Group", "pagerange": "295-302", "id_number": "CaltechAUTHORS:20140424-093502261", "issn": "1755-4330", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140424-093502261", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "NSF", "grant_number": "CMMI-1266402" }, { "agency": "University of California, Riverside" }, { "agency": "University of California Regents" }, { "agency": "European Research Council (ERC)", "grant_number": "248919" }, { "agency": "Nanosystems Initiative Munich" }, { "agency": "Elite Network of Bayern" }, { "agency": "Bavaria California Technology Center (BaCaTe)" } ] }, "doi": "10.1038/NCHEM.1869", "primary_object": { "basename": "nchem.1869-s1.pdf", "url": "https://authors.library.caltech.edu/records/fhx14-66450/files/nchem.1869-s1.pdf" }, "related_objects": [ { "basename": "nchem.1869-s2.mov", "url": "https://authors.library.caltech.edu/records/fhx14-66450/files/nchem.1869-s2.mov" }, { "basename": "nchem.1869-s3.mov", "url": "https://authors.library.caltech.edu/records/fhx14-66450/files/nchem.1869-s3.mov" }, { "basename": "nchem.1869-s4.mov", "url": "https://authors.library.caltech.edu/records/fhx14-66450/files/nchem.1869-s4.mov" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Weitz, Maximilian; Kim, Jongmin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qbzx4-yr147", "eprint_id": 43732, "eprint_status": "archive", "datestamp": "2023-08-19 22:23:49", "lastmod": "2023-10-25 23:49:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Srinivas-N", "name": { "family": "Srinivas", "given": "Niranjan" } }, { "id": "Ouldridge-T-E", "name": { "family": "Ouldridge", "given": "Thomas E." } }, { "id": "\u0160ulc-P", "name": { "family": "\u0160ulc", "given": "Petr" } }, { "id": "Schaeffer-J-M", "name": { "family": "Schaeffer", "given": "Joseph M." } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Louis-A-A", "name": { "family": "Louis", "given": "Ard A." } }, { "id": "Doye-J-P-K", "name": { "family": "Doye", "given": "Jonathan P. K." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "On the biophysics and kinetics of toehold-mediated DNA strand displacement", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 The Author(s). Published by Oxford University Press.\n\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/\nby-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nReceived March 29, 2013; Revised July 18, 2013; Accepted August 14, 2013; Published online 9 September 2013.\n\nThe authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.\n\nThe authors thank Zhen-Gang Wang, Andrew J.\nTurberfield, David Yu Zhang, Niles A. Pierce, Brian R.\nWolfe, David Soloveichik and Georg Seelig for helpful\ndiscussions. The authors thank the anonymous referees\nfor feedback, which significantly improved this work.\n\nFunding: National Science Foundation [CCF-0832824]; the\nEngineering and Physical Sciences Research Council\n[EP/I001352/1]; the Gordon and Betty Moore\nFoundation through the Caltech Programmable\nMolecular Technology Initiative; the Scatcherd\nEuropean Trust; and University College, Oxford.\nFunding for open access charge: 'Caltech Programmable\nMolecular Technology Initiative', through the Gordon\nand Betty Moore Foundation.\n\nConflict of interest statement. None declared.\n\nPublished - Nucl._Acids_Res.-2013-Srinivas-10641-58.pdf
Supplemental Material - nar-00936-f-2013-File028.pdf
", "abstract": "Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.", "date": "2013-12", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "41", "number": "22", "publisher": "Oxford University Press", "pagerange": "10641-10658", "id_number": "CaltechAUTHORS:20140210-082347979", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140210-082347979", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Engineering and Physical Sciences Research Council (EPSRC)", "grant_number": "EP/I001352/1" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Caltech Programmable Molecular Technology Initiative" }, { "agency": "Scatcherd European Trust" }, { "agency": "University College Oxford" } ] }, "doi": "10.1093/nar/gkt801", "pmcid": "PMC3905871", "primary_object": { "basename": "Nucl._Acids_Res.-2013-Srinivas-10641-58.pdf", "url": "https://authors.library.caltech.edu/records/qbzx4-yr147/files/Nucl._Acids_Res.-2013-Srinivas-10641-58.pdf" }, "related_objects": [ { "basename": "nar-00936-f-2013-File028.pdf", "url": "https://authors.library.caltech.edu/records/qbzx4-yr147/files/nar-00936-f-2013-File028.pdf" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Srinivas, Niranjan; Ouldridge, Thomas E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/mc03v-3h408", "eprint_id": 41623, "eprint_status": "archive", "datestamp": "2023-08-19 20:12:23", "lastmod": "2023-10-24 23:53:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-D-Y", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Hariadi-R-F", "name": { "family": "Hariadi", "given": "Rizal F." } }, { "id": "Choi-H-M-T", "name": { "family": "Choi", "given": "Harry M. T." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Integrating DNA strand-displacement circuitry with DNA tile self-assembly", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 Macmillan Publishers Limited.\n\nReceived 5 Sep 2012; Accepted 1 May 2013; Published 12 Jun 2013.\n\nThis work is licensed under a Creative Commons Attribution-\nNonCommercial-NoDerivs 3.0 Unported License. To view a copy of\nthis license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/\n\nThis work was supported in part by National Science Foundations grants 0832824,\n0829805, and 0728703 to E.W. This work was supported in part by a Hertz Foundation\ngraduate fellowship, a Howard Hughes Medical Institute postdoctoral fellowship as part\nof the Life Sciences Research Foundation program, and NIH Award 1K99EB015331 to\nD.Y.Z.\nAuthor contributions:\nD.Y.Z., R.F.H. and H.M.T.C. conceived and designed the experiments; D.Y.Z. and R.F.H.\nperformed the experiments and analyzed the data; D.Y.Z. and E.W. wrote the paper;\nE.W. guided the research.\n\nPublished - Zhang_2013p1965.pdf
Supplemental Material - ncomms2965-s1.pdf
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Supplemental Material - ncomms2965-s5.mov
", "abstract": "DNA nanotechnology has emerged as a reliable and programmable way of controlling matter\nat the nanoscale through the specificity of Watson\u2013Crick base pairing, allowing both complex\nself-assembled structures with nanometer precision and complex reaction networks implementing\ndigital and analog behaviors. Here we show how two well-developed frameworks,\nDNA tile self-assembly and DNA strand-displacement circuits, can be systematically\nintegrated to provide programmable kinetic control of self-assembly. We demonstrate the\ntriggered and catalytic isothermal self-assembly of DNA nanotubes over 10 \u00b5m long from\nprecursor DNA double-crossover tiles activated by an upstream DNA catalyst network.\nIntegrating more sophisticated control circuits and tile systems could enable precise spatial\nand temporal organization of dynamic molecular structures.", "date": "2013-06", "date_type": "published", "publication": "Nature Communications", "volume": "4", "number": "6", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 1965", "id_number": "CaltechAUTHORS:20131002-145120699", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131002-145120699", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0832824" }, { "agency": "NSF", "grant_number": "0829805" }, { "agency": "NSF", "grant_number": "0728703" }, { "agency": "Fannie and John Hertz Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "1K99EB015331" } ] }, "doi": "10.1038/ncomms2965", "pmcid": "PMC3709499", "primary_object": { "basename": "Zhang_2013p1965.pdf", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/Zhang_2013p1965.pdf" }, "related_objects": [ { "basename": "ncomms2965-s1.pdf", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/ncomms2965-s1.pdf" }, { "basename": "ncomms2965-s2.mov", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/ncomms2965-s2.mov" }, { "basename": "ncomms2965-s3.mov", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/ncomms2965-s3.mov" }, { "basename": "ncomms2965-s4.mov", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/ncomms2965-s4.mov" }, { "basename": "ncomms2965-s5.mov", "url": "https://authors.library.caltech.edu/records/mc03v-3h408/files/ncomms2965-s5.mov" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Zhang, David Yu; Hariadi, Rizal F.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/esd5f-zr675", "eprint_id": 36616, "eprint_status": "archive", "datestamp": "2023-08-19 14:08:32", "lastmod": "2023-10-20 23:24:08", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Woods-D", "name": { "family": "Woods", "given": "Damien" } }, { "id": "Chen-H-L", "name": { "family": "Chen", "given": "Ho-Lin" } }, { "id": "Goodfriend-S", "name": { "family": "Goodfriend", "given": "Scott" } }, { "id": "Dabby-N", "name": { "family": "Dabby", "given": "Nadine" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Yin-P", "name": { "family": "Yin", "given": "Peng" } } ] }, "title": "Active Self-Assembly of Algorithmic Shapes and Patterns in Polylogarithmic Time", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2013 held by the author/owner(s). ITCS'13, January 9\u201312, 2013, Berkeley, California, USA. ACM 978-1-4503-1859-4/13/01. Supported by NSF grants CCF-1219274, CCF-1162589, and 0832824|the Molecular Programming Project, an NSF Graduate Fellowship, and The Caltech Center for Biological Circuit Design. Many thanks to Niles Pierce and Patrick Mullen for valuable discussions.\n\nSubmitted - 1301.2626v1.pdf
", "abstract": "We describe a computational model for studying the complexity of self-assembled structures with active molecular components. Our model captures notions of growth and movement ubiquitous in biological systems. The model is inspired by biology's fantastic ability to assemble biomolecules that form systems with complicated structure and dynamics, from molecular motors that walk on rigid tracks and proteins that dynamically alter the structure of the cell during mitosis, to embryonic development where large-scale complicated organisms efficiently grow from a single cell. Using this active self-assembly model, we show how to efficiently self-assemble shapes and patterns from simple monomers. For example, we show how to grow a line of monomers in time and number of monomer states that is merely logarithmic in the length of the line.\nOur main results show how to grow arbitrary connected two-dimensional geometric shapes and patterns in expected time that is polylogarithmic in the size of the shape, plus roughly the time required to run a Turing machine deciding whether or not a given pixel is in the shape. We do this while keeping the number of monomer types logarithmic in shape size, plus those monomers required by the Kolmogorov complexity of the shape or pattern. This work thus highlights the efficiency advantages of active self-assembly over passive self-assembly and motivates experimental effort to construct general-purpose active molecular self-assembly systems.", "date": "2013-01", "date_type": "published", "publisher": "ACM", "place_of_pub": "New York, NY", "pagerange": "353-354", "id_number": "CaltechAUTHORS:20130128-100842529", "isbn": "978-1-4503-1859-4", "book_title": "Proceedings of the 4th conference on Innovations in Theoretical Computer Science", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130128-100842529", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-1219274" }, { "agency": "NSF", "grant_number": "CCF-1162589" }, { "agency": "NSF Molecular Programming Project", "grant_number": "0832824" }, { "agency": "NSF Graduate Fellowship" }, { "agency": "Caltech Center for Biological Circuit Design" } ] }, "doi": "10.1145/2422436.2422476", "primary_object": { "basename": "1301.2626v1.pdf", "url": "https://authors.library.caltech.edu/records/esd5f-zr675/files/1301.2626v1.pdf" }, "resource_type": "book_section", "pub_year": "2013", "author_list": "Woods, Damien; Chen, Ho-Lin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5mdh8-pp183", "eprint_id": 46019, "eprint_status": "archive", "datestamp": "2023-08-19 14:03:24", "lastmod": "2024-01-13 16:05:28", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Evans-C-G", "name": { "family": "Evans", "given": "Constantine G." }, "orcid": "0000-0002-7053-1670" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "DNA Sticky End Design and Assignment for Robust Algorithmic Self-assembly", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2013 Springer International Publishing Switzerland.\n\nAccepted Version - StickyDesign2013.pdf
", "abstract": "A major challenge in practical DNA tile self-assembly is the minimization of errors. Using the kinetic Tile Assembly Model, a theoretical model of self-assembly, it has been shown that errors can be reduced through abstract tile set design. In this paper, we instead investigate the effects of \"sticky end\" sequence choices in systems using the kinetic model along with the nearest-neighbor model of DNA interactions. We show that both the sticky end sequences present in a system and their positions in the system can significantly affect error rates, and propose algorithms for sequence design and assignment.", "date": "2013", "date_type": "published", "publisher": "Springer", "place_of_pub": "Cham, Switzerland", "pagerange": "61-75", "id_number": "CaltechAUTHORS:20140530-150254025", "isbn": "978-3-319-01927-7", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140530-150254025", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" } } ] }, "doi": "10.1007/978-3-319-01928-4_5", "primary_object": { "basename": "StickyDesign2013.pdf", "url": "https://authors.library.caltech.edu/records/5mdh8-pp183/files/StickyDesign2013.pdf" }, "resource_type": "book_section", "pub_year": "2013", "author_list": "Evans, Constantine G. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1m0y1-2zx98", "eprint_id": 32911, "eprint_status": "archive", "datestamp": "2023-08-22 06:14:29", "lastmod": "2023-10-18 16:29:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Subsoontorn-Pakpoom", "name": { "family": "Subsoontorn", "given": "Pakpoom" } }, { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Ensemble Bayesian Analysis of Bistability in a Synthetic Transcriptional Switch", "ispublished": "pub", "full_text_status": "public", "keywords": "in vitro; synthetic biology; systems biology; reductionism; transcriptional circuits", "note": "\u00a9 2012 American Chemical Society. \n\nReceived: March 23, 2012. Publication Date (Web): June 13, 2012. \n\nThis work was supported by the National Science Foundation awards 0103002, 0608889, and 0832824 (The Molecular Programming Project); the Human Frontiers Science Program award RGY0074/2006-C; and the Caltech Center for Biological Circuit Design. A preliminary version of this work appeared in ref 80. \n\nP.S., J.K., and E.W. designed research; P.S. performed experiments; P.S., J.K., and E.W. analyzed data; P.S., J.K., and E.W. wrote the manuscript. \n\nThe authors declare no competing financial interest.\n\nSupplemental Material - sb300018h_si_001.pdf
", "abstract": "An overarching goal of synthetic and systems biology is to engineer and understand complex biochemical systems by rationally designing and analyzing their basic component interactions. Practically, the extent to which such reductionist approaches can be applied is unclear especially as the complexity of the system increases. Toward gradually increasing the complexity of systematically engineered systems, programmable synthetic circuits operating in cell-free in vitro environments offer a valuable testing ground for principles for the design, characterization, and analysis of complex biochemical systems. Here we illustrate this approach using in vitro transcriptional circuits (\"genelets\") while developing an activatable transcriptional switch motif and configuring it as a bistable autoregulatory circuit, using just four synthetic DNA strands and three essential enzymes, bacteriophage T7 RNA polymerase, Escherichia coli ribonuclease H, and ribonuclease R. Fulfilling the promise of predictable system design, the thermodynamic and kinetic constraints prescribed at the sequence level were enough to experimentally demonstrate intended bistable dynamics for the synthetic autoregulatory switch. A simple mathematical model was constructed based on the mechanistic understanding of elementary reactions, and a Monte Carlo Bayesian inference approach was employed to find parameter sets compatible with a training set of experimental results; this ensemble of parameter sets was then used to predict a test set of additional experiments with reasonable agreement and to provide a rigorous basis for confidence in the mechanistic model. Our work demonstrates that programmable in vitro biochemical circuits can serve as a testing ground for evaluating methods for the design and analysis of more complex biochemical systems such as living cells.", "date": "2012-08", "date_type": "published", "publication": "ACS Synthetic Biology", "volume": "1", "number": "8", "publisher": "American Chemical Society", "pagerange": "299-316", "id_number": "CaltechAUTHORS:20120803-102247969", "issn": "2161-5063", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120803-102247969", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CBET-0103002" }, { "agency": "NSF", "grant_number": "CBET-0608889" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" }, { "agency": "Caltech Center for Biological Circuit Design" } ] }, "doi": "10.1021/sb300018h", "primary_object": { "basename": "sb300018h_si_001.pdf", "url": "https://authors.library.caltech.edu/records/1m0y1-2zx98/files/sb300018h_si_001.pdf" }, "resource_type": "article", "pub_year": "2012", "author_list": "Subsoontorn, Pakpoom; Kim, Jongmin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r3nca-b1y45", "eprint_id": 32617, "eprint_status": "archive", "datestamp": "2023-08-19 11:28:49", "lastmod": "2023-10-18 14:36:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Evans-C-G", "name": { "family": "Evans", "given": "Constantine G." }, "orcid": "0000-0002-7053-1670" }, { "id": "Hariadi-R-F", "name": { "family": "Hariadi", "given": "Rizal F." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Direct Atomic Force Microscopy Observation of DNA Tile Crystal Growth at the Single-Molecule Level", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2012 American Chemical Society.\n\nPublished In Issue June 27, 2012; Article ASAP June 13, 2012; Received: February 13, 2012.\n\nWe thank Christina Wright for prototype software for analyzing AFM movies, and Shaun Lee for discussions regarding AFM movies of DNA tiles. We acknowledge National Science Foundation (NSF) Awards 0832824 (\"The Molecular Programming Project\") and 0622254.\n\nPublished - Evans2012p18912J_Am_Chem_Soc.pdf
Supplemental Material - ja301026z_si_001.avi
", "abstract": "While the theoretical implications of models of DNA tile self-assembly have been extensively researched and such models have been used to design DNA tile systems for use in experiments, there has been little research testing the fundamental assumptions of those models. In this paper, we use direct observation of individual tile attachments and detachments of two DNA tile systems on a mica surface imaged with an atomic force microscope (AFM) to compile statistics of tile attachments and detachments. We show that these statistics fit the widely used kinetic Tile Assembly Model and demonstrate AFM movies as a viable technique for directly investigating DNA tile systems during growth rather than after assembly.", "date": "2012-06-27", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "134", "number": "25", "publisher": "American Chemical Society", "pagerange": "10485-10492", "id_number": "CaltechAUTHORS:20120720-132124836", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120720-132124836", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0832824" }, { "agency": "NSF", "grant_number": "0622254" } ] }, "doi": "10.1021/ja301026z", "primary_object": { "basename": "Evans2012p18912J_Am_Chem_Soc.pdf", "url": "https://authors.library.caltech.edu/records/r3nca-b1y45/files/Evans2012p18912J_Am_Chem_Soc.pdf" }, "related_objects": [ { "basename": "ja301026z_si_001.avi", "url": "https://authors.library.caltech.edu/records/r3nca-b1y45/files/ja301026z_si_001.avi" } ], "resource_type": "article", "pub_year": "2012", "author_list": "Evans, Constantine G.; Hariadi, Rizal F.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xhj14-45j48", "eprint_id": 32056, "eprint_status": "archive", "datestamp": "2023-08-19 11:05:53", "lastmod": "2023-10-17 22:23:53", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Simple evolution of complex crystal species", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2012 Springer Science+Business Media B.V. \n\nPublished online: 5 February 2012.", "abstract": "Cairns-Smith has proposed that life began as structural patterns in clays that self-replicated during cycles of crystal growth and fragmentation. Complex, evolved crystal forms could then have catalyzed the formation of a more advanced genetic material. A crucial weakness of this theory is that it is unclear how complex crystals might arise through Darwinian evolution and selection. Here we investigate whether complex crystal patterns could evolve using a model system for crystal growth, DNA tile crystals, that is amenable to both theoretical and experimental inquiry. It was previously shown that in principle, the evolution of crystals assembled from a set of thousands of DNA tile types under very specific environmental conditions could produce arbitrarily complex patterns. Here we show that evolution driven only by the dearth of one monomer type could produce complex crystals from just 12 monomer types. When a monomer type is rare, crystals that use few of this monomer type are selected for. We use explicit enumeration to show that there are situations in which crystal species that use a particular monomer type less frequently will grow faster, yet to do so requires that the information contained in the crystal become more complex. We show that this feature of crystal organization could allow more complex crystal morphologies to be selected for in the right environment, using both analysis in a simple model of self-assembly and stochastic kinetic simulations of crystal growth. The proposed mechanism of evolution is simple enough to test experimentally and is sufficiently general that it may apply to other DNA tile crystals or even to natural crystals, suggesting that complex crystals could evolve from simple starting materials because of relative differences in concentrations of the materials needed for growth.", "date": "2012-06", "date_type": "published", "publication": "Natural Computing", "volume": "11", "number": "2", "publisher": "Springer", "pagerange": "187-197", "id_number": "CaltechAUTHORS:20120625-095143843", "issn": "1567-7818", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120625-095143843", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1007/s11047-011-9302-9", "resource_type": "article", "pub_year": "2012", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kb4e2-pct57", "eprint_id": 31493, "eprint_status": "archive", "datestamp": "2023-08-22 05:29:49", "lastmod": "2023-10-17 16:37:45", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Robust self-replication of combinatorial information via crystal growth and scission", "ispublished": "pub", "full_text_status": "public", "keywords": "algorithmic self-assembly; DNA nanotechnology; self-assembly", "note": "\u00a9 2012 National Academy of Sciences. Freely available online through the PNAS open access option. This article is a PNAS Direct Submission. Edited by Gerald F. Joyce, The Scripps Research Institute, La Jolla, CA, and approved February 21, 2012 (received for review October 31, 2011).\nPublished online before print April 9, 2012.\nThe authors thank Graham Cairns-Smith, Rizal Hariadi,\nAndrew Ellington, Andrew Turberfield, Damien Woods, and Paul Rothemund for discussion and suggestions. The authors acknowledge grants from the Miller Institute of Basic Science to R.S. and National Aeronautics and Space\nAdministration Astrobiology Grant NNG06GA50 and National Science Foundation CCF: \"The Molecular Programming Project,\" Grant 0832824 to E.W. Author contributions: R.S., B.Y., and E.W. designed research; R.S. performed research; R.S. and B.Y. analyzed data; and R.S., B.Y., and E.W. wrote the paper. The authors declare no conflict of interest.\n\nPublished - Schulman2012p18057P_Natl_Acad_Sci_Usa.pdf
", "abstract": "Understanding how a simple chemical system can accurately replicate combinatorial information, such as a sequence, is an important question for both the study of life in the universe and for the development of evolutionary molecular design techniques. During biological sequence replication, a nucleic acid polymer serves as a template for the enzyme-catalyzed assembly of a complementary sequence. Enzymes then separate the template and complement before the next round of replication. Attempts to understand how replication could occur more simply, such as without enzymes, have largely focused on developing minimal versions of this replication process. Here we describe how a different mechanism, crystal growth and scission, can accurately replicate chemical sequences without enzymes. Crystal growth propagates a sequence of bits while mechanically-induced scission creates new growth fronts. Together, these processes exponentially increase the number of crystal sequences. In the system we describe, sequences are arrangements of DNA tile monomers within ribbon-shaped crystals. 99.98% of bits are copied correctly and 78% of 4-bit sequences are correct after two generations; roughly 40 sequence copies are made per growth front per generation. In principle, this process is accurate enough for 1,000-fold replication of 4-bit sequences with 50% yield, replication of longer sequences, and Darwinian evolution. We thus demonstrate that neither enzymes nor covalent bond formation are required for robust chemical sequence replication. The form of the replicated information is also compatible with the replication and evolution of a wide class of materials with precise nanoscale geometry such as plasmonic nanostructures or heterogeneous protein assemblies.", "date": "2012-04-24", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "109", "number": "17", "publisher": "National Academy of Sciences", "pagerange": "6405-6410", "id_number": "CaltechAUTHORS:20120516-075032994", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120516-075032994", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Miller Institute of Basic Science" }, { "agency": "NASA Astrobiology", "grant_number": "NNG06GA50" }, { "agency": "NSF", "grant_number": "CCF-0832824" } ] }, "doi": "10.1073/pnas.1117813109", "pmcid": "PMC3340064", "primary_object": { "basename": "Schulman2012p18057P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/kb4e2-pct57/files/Schulman2012p18057P_Natl_Acad_Sci_Usa.pdf" }, "resource_type": "article", "pub_year": "2012", "author_list": "Schulman, Rebecca; Yurke, Bernard; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3xw46-ycg28", "eprint_id": 27324, "eprint_status": "archive", "datestamp": "2023-08-22 03:54:21", "lastmod": "2023-10-24 17:04:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Franco-E", "name": { "family": "Franco", "given": "Elisa" }, "orcid": "0000-0003-1103-2668" }, { "id": "Friedrichs-Eike", "name": { "family": "Friedrichs", "given": "Eike" } }, { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Jungmann-R", "name": { "family": "Jungmann", "given": "Ralf" } }, { "id": "Murray-R-M", "name": { "family": "Murray", "given": "Richard M." }, "orcid": "0000-0002-5785-7481" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Simmel-F-C", "name": { "family": "Simmel", "given": "Friedrich C." }, "orcid": "0000-0003-3829-3446" } ] }, "title": "Timing molecular motion and production with a synthetic transcriptional clock", "ispublished": "pub", "full_text_status": "public", "keywords": "cell-free circuits; modularity; genelets; DNA nanotechnology", "note": "\u00a9 2011 by the National Academy of Sciences. Freely available online through the PNAS open access option.\n\n\nEdited by David Baker, University of Washington, Seattle, WA, and approved August 9, 2011 (received for review January 17, 2011).\nWe are especially grateful to Eric Klavins for coining\nthe irresistible moniker \"genelets,\" to Maximilian Weitz for control measurements,\nand to Franco Blanchini for mathematical advice. The authors\nacknowledge financial support by the Human Frontier Science Program\n(HFSP) grant no. RGY 74/2006, the European Commission FP7 grant no.\n248919 (BACTOCOM), the National Science Foundation (NSF) grants nos.\nNIRT-0608889 and CCF-0832824 (The Molecular Programming Project), the\nInstitute for Collaborative Biotechnologies (grant DAAD19-03-D-0004 from\nthe Army Research Office), and the Nanosystems Initiative Munich (NIM).\n\nAuthor contributions: E. Franco, E. Friedrichs, J.K., E.W., and F.C.S. designed research; E. Franco\nand E. Friedrichs performed research; E. Franco, E. Friedrichs, J.K., R.J., R.M., E.W., and F.C.S.\nanalyzed data; and E. Franco, E. Friedrichs, J.K., R.J., E.W., and F.C.S. wrote the paper.\n\nPublished - PNAS-2011-Franco-E784-93_1_.pdf
Supplemental Material - Appendix.pdf
", "abstract": "The realization of artificial biochemical reaction networks with unique functionality is one of the main challenges for the development of synthetic biology. Due to the reduced number of components, biochemical circuits constructed in vitro promise to be more amenable to systematic design and quantitative assessment than circuits embedded within living organisms. To make good on that promise, effective methods for composing subsystems into larger systems are needed. Here we used an artificial biochemical oscillator based on in vitro transcription and RNA degradation reactions to drive a variety of \"load\" processes such as the operation of a DNA-based nanomechanical device (\"DNA tweezers\") or the production of a functional RNA molecule (an aptamer for malachite green). We implemented several mechanisms for coupling the load processes to the oscillator circuit and compared them based on how much the load affected the frequency and amplitude of the core oscillator, and how much of the load was effectively driven. Based on heuristic insights and computational modeling, an \"insulator circuit\" was developed, which strongly reduced the detrimental influence of the load on the oscillator circuit. Understanding how to design effective insulation between biochemical subsystems will be critical for the synthesis of larger and more complex systems.", "date": "2011-10-04", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "108", "number": "40", "publisher": "National Academy of Sciences", "pagerange": "E784-E793", "id_number": "CaltechAUTHORS:20111020-091851903", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-091851903", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Human Frontier Science Program", "grant_number": "RGY 74/2006" }, { "agency": "European Research Council (ERC)", "grant_number": "248919" }, { "agency": "NSF", "grant_number": "CBET-0608889" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Army Research Office (ARO)", "grant_number": "DAAD19-03-D-0004" }, { "agency": "Nanosystems Initiative Munich" } ] }, "doi": "10.1073/pnas.1100060108", "pmcid": "PMC3189071", "primary_object": { "basename": "Appendix.pdf", "url": "https://authors.library.caltech.edu/records/3xw46-ycg28/files/Appendix.pdf" }, "related_objects": [ { "basename": "PNAS-2011-Franco-E784-93_1_.pdf", "url": "https://authors.library.caltech.edu/records/3xw46-ycg28/files/PNAS-2011-Franco-E784-93_1_.pdf" } ], "resource_type": "article", "pub_year": "2011", "author_list": "Franco, Elisa; Friedrichs, Eike; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3zjx7-mx574", "eprint_id": 24716, "eprint_status": "archive", "datestamp": "2023-08-22 03:39:51", "lastmod": "2023-10-24 14:51:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "A simple DNA gate motif for synthesizing large-scale circuits", "ispublished": "pub", "full_text_status": "public", "keywords": "nucleic acids; synthetic biology; strand displacement circuits; molecular programming", "note": "\u00a9 2011 The Royal Society. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived December 20, 2010. Accepted January 14, 2011. Published online before print February 4, 2011. \n\nThe authors thank Dave Zhang for discussion of the catalytic mechanism, Marc Riedel for providing example netlists from logic synthesis benchmarks, Virgil Griffith for suggesting useful techniques for DNA sequence design, Ho-Lin Chen and Shuki Bruck for suggesting the connection to relay circuits, David Soloveichik for Mathematica code simulating mass-action chemical reaction networks, and Georg Seelig, Bernard Yurke, and everyone else for discussions and support. This work has been supported by NSF grant nos. 0728703, and 0832824 (The Molecular Programming Project) and HFSP award no. RGY0074/2006-C. A preliminary version of this paper appeared as Qian & Winfree [64].\n\nPublished - Qian2011p15422J_R_Soc_Interface.pdf
", "abstract": "The prospects of programming molecular systems to perform complex autonomous tasks have motivated research into the design of synthetic biochemical circuits. Of particular interest to us are cell-free nucleic acid systems that exploit non-covalent hybridization and strand displacement\nreactions to create cascades that implement digital and analogue circuits. To date, circuits involving at most tens of gates have been demonstrated experimentally. Here, we\npropose a simple DNA gate architecture that appears suitable for practical synthesis of large-scale circuits involving possibly thousands of gates.", "date": "2011-09-07", "date_type": "published", "publication": "Journal of the Royal Society Interface", "volume": "8", "number": "62", "publisher": "The Royal Society", "pagerange": "1281-1297", "id_number": "CaltechAUTHORS:20110805-144518758", "issn": "1742-5689", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110805-144518758", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" } ] }, "doi": "10.1098/rsif.2010.0729", "primary_object": { "basename": "Qian2011p15422J_R_Soc_Interface.pdf", "url": "https://authors.library.caltech.edu/records/3zjx7-mx574/files/Qian2011p15422J_R_Soc_Interface.pdf" }, "resource_type": "article", "pub_year": "2011", "author_list": "Qian, Lulu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fryqk-9d474", "eprint_id": 24613, "eprint_status": "archive", "datestamp": "2023-08-22 03:15:27", "lastmod": "2023-10-23 23:30:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" } ] }, "title": "Neural network computation with DNA strand displacement cascades", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Information technology; Neuroscience; Biotechnology; Molecular biology", "note": "\u00a9 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. \n\nReceived 31 December 2010; accepted 31 May 2011.\nPublished online 20 July 2011.\nWe thank P. Rothemund, P. Yin, D. Woods, D. Soloveichik and\nN. Dabby for comments on the manuscript. We also thank R. Murray for the use of experimental facilities. This work was supported by the NSF (grant nos 0728703 and 0832824 (The Molecular Programming Project)) and by HFSP award no. RGY0074/2006-C.\n\nAuthor Contributions: L.Q. designed the system, performed the experiments and\nanalysed the data; L.Q. and E.W. performed the in silico training and wrote the\nmanuscript; E.W. guided the project and discussed the design and the data; and J.B.\ninitiated and guided the project, and discussed the manuscript.", "abstract": "The impressive capabilities of the mammalian brain\u2014ranging from perception, pattern recognition and memory formation to decision making and motor activity control\u2014have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control. Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the 'intelligent' behaviour required for survival. However, the study of how molecules can 'think' has not produced an equal variety of computational models and applications of artificial chemical systems. Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo and the synthesis of artificial chemical analogues has been proposed theoretically, experimental work has so far fallen short of fully implementing even a single neuron. Here, building on the richness of DNA computing and strand displacement circuitry, we show how molecular systems can exhibit autonomous brain-like behaviours. Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, we systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks. Our approach even allows us to implement a Hopfield associative memory with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern. Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment.", "date": "2011-07-21", "date_type": "published", "publication": "Nature", "volume": "475", "number": "7356", "publisher": "Nature Publishing Group", "pagerange": "368-372", "id_number": "CaltechAUTHORS:20110801-112437228", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110801-112437228", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0728703" }, { "agency": "NSF", "grant_number": "0832824" }, { "agency": "HFSP", "grant_number": "RGY0074/ 2006-C" } ] }, "doi": "10.1038/nature10262", "resource_type": "article", "pub_year": "2011", "author_list": "Qian, Lulu; Winfree, Erik; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/akcvd-thp06", "eprint_id": 24047, "eprint_status": "archive", "datestamp": "2023-08-19 07:05:28", "lastmod": "2023-10-23 20:16:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2011 American Association for the Advancement of Science. Received for publication 16 November 2010. \nAccepted for publication 15 April 2011. \nWe thank D. Y. Zhang for providing\nuseful comments on the manuscript. Supported by\nNSF grants 0728703 and 0832824 (Molecular\nProgramming Project) and Human Frontier Science\nProgram award RGY0074/2006-C.", "abstract": "To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.", "date": "2011-06-03", "date_type": "published", "publication": "Science", "volume": "332", "number": "6034", "publisher": "American Association for the Advancement of Science", "pagerange": "1196-1201", "id_number": "CaltechAUTHORS:20110617-132231112", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110617-132231112", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0728703" }, { "agency": "NSF", "grant_number": "0832824" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" } ] }, "doi": "10.1126/science.1200520", "resource_type": "article", "pub_year": "2011", "author_list": "Qian, Lulu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jm59x-m4z18", "eprint_id": 31573, "eprint_status": "archive", "datestamp": "2023-08-19 06:57:53", "lastmod": "2023-10-17 18:41:04", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Densmore-D", "name": { "family": "Densmore", "given": "Douglas" } }, { "id": "Horowitz-M", "name": { "family": "Horowitz", "given": "Mark" } }, { "id": "Krishnaswamy-S", "name": { "family": "Krishnaswamy", "given": "Smita" } }, { "id": "Shen-X", "name": { "family": "Shen", "given": "Xiling" } }, { "id": "Arkin-A", "name": { "family": "Arkin", "given": "Adam" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Voigt-C", "name": { "family": "Voigt", "given": "Chris" } } ] }, "title": "Joint DAC/IWBDA special session design and synthesis of biological circuits", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "bio-design automation, genetic compiler, chemical reaction\nnetworks, molecular computation, biological parts", "note": "\u00a9 2011 ACM.", "abstract": "With the growing complexity of synthetic biological circuits, robust and systematic methods are needed for design and test. Leveraging lessons learned from the semiconductor and design automation industries, synthetic biologists are starting to adopt computer-aided design and verification software with some success. However, due to the great challenges associated with designing synthetic biological circuits, this nascent approach has to address many problems not present in electronic circuits. In this session, three leading synthetic biologists will share how they have developed software tools to help design and verify their synthetic circuits, the unique challenges they face, and their insights into the next generation of tools for synthetic biology.", "date": "2011-06", "date_type": "published", "publisher": "Association for Computing Machinery (ACM)", "place_of_pub": "New York", "pagerange": "114-115", "id_number": "CaltechAUTHORS:20120521-113649301", "isbn": "978-1-4503-0636-2", "book_title": "Proceedings of the 48th Design Automation Conference", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120521-113649301", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1145/2024724.2024750", "resource_type": "book_section", "pub_year": "2011", "author_list": "Densmore, Douglas; Horowitz, Mark; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3jcyw-ct451", "eprint_id": 23200, "eprint_status": "archive", "datestamp": "2023-08-22 02:00:53", "lastmod": "2023-10-23 18:03:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Synthetic in vitro transcriptional oscillators", "ispublished": "pub", "full_text_status": "public", "keywords": "cell free; in vitro; oscillation; synthetic biology; transcriptional circuits", "note": "\u00a9 2011 EMBO and Macmillan Publishers Limited.\n\nMolecular Systems Biology is an open-access journal\npublished by European Molecular Biology Organization\nand Nature Publishing Group. This work is licensed under a\nCreative Commons Attribution-Noncommercial-No Derivative\nWorks 3.0 Unported License.\n\nReceived 3 August 2010; Accepted 13 December 2010; Published online 1 February 2011. We thank P Subsoontorn, E Franco, R Murray, E Friedrichs,\nR Jungmann, F Simmel, E Klavins, P Rothemund, G Seelig, R Hariadi, D Zhang, and B Yurke for discussion. This study was supported by ONR YIP award no. N000140110813; NSF award nos. 0103002, 0113443,0608889, 0832824 (The Molecular Programming Project); HFSP award no. RGY0074/2006-C, and the Caltech Center for Biological Circuit Design. The experimental work described here was initially reported in\nKim (2007). As we were preparing this manuscript for publication, we became aware of another successful effort to construct a cell-free in vitro biochemical oscillator (Montagne et al, 2011). Author contributions: JK and EW designed the experiments; JK conducted the experiments; JK and EW analyzed the data; JK and EW wrote the paper.\n\nPublished - Kim2011p13226Mol_Syst_Biol.pdf
Supplemental Material - msb2010119-s1.pdf
Supplemental Material - msb2010119-s2.zip
", "abstract": "The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells.", "date": "2011-02", "date_type": "published", "publication": "Molecular Systems Biology", "volume": "7", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 465", "id_number": "CaltechAUTHORS:20110401-112412294", "issn": "1744-4292", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110401-112412294", "rights": "This is an open-access article distributed under the terms of the Creative Commons Attribution\nNoncommercial No Derivative Works 3.0 Unported License, which permits distribution and reproduction\ninanymedium,providedtheoriginalauthorandsourceare credited.This licensedoesnotpermitcommercial\nexploitation or the creation of derivativeworks without specific permission.", "funders": { "items": [ { "agency": "Office of Naval Research (ONR)", "grant_number": "N000140110813" }, { "agency": "NSF", "grant_number": "CBET-0103002" }, { "agency": "NSF", "grant_number": "CCF-0113443" }, { "agency": "NSF", "grant_number": "CBET-0608889" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" }, { "agency": "Caltech Center for Biological Circuit Design" } ] }, "doi": "10.1038/msb.2010.119", "pmcid": "PMC3063688", "primary_object": { "basename": "Kim2011p13226Mol_Syst_Biol.pdf", "url": "https://authors.library.caltech.edu/records/3jcyw-ct451/files/Kim2011p13226Mol_Syst_Biol.pdf" }, "related_objects": [ { "basename": "msb2010119-s1.pdf", "url": "https://authors.library.caltech.edu/records/3jcyw-ct451/files/msb2010119-s1.pdf" }, { "basename": "msb2010119-s2.zip", "url": "https://authors.library.caltech.edu/records/3jcyw-ct451/files/msb2010119-s2.zip" } ], "resource_type": "article", "pub_year": "2011", "author_list": "Kim, Jongmin and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qrkyb-dzm06", "eprint_id": 27325, "eprint_status": "archive", "datestamp": "2023-08-22 01:49:56", "lastmod": "2023-10-24 17:04:07", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Subsoontorn-Pakpoom", "name": { "family": "Subsoontorn", "given": "Pakpoom" } }, { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Bistability of an In Vitro Synthetic Autoregulatory Switch", "ispublished": "unpub", "full_text_status": "public", "keywords": "Molecular Networks (q-bio.MN); Biomolecules (q-bio.BM); Quantitative Methods (q-bio.QM)", "note": "Submitted - self-activating-switch2011.pdf
", "abstract": "The construction of synthetic biochemical circuits is an essential step for developing quantitative understanding\nof information processing in natural organisms. Here, we report construction and analysis of an in vitro circuit with\npositive autoregulation that consists of just four synthetic DNA strands and three enzymes, bacteriophage T7 RNA\npolymerase, Escherichia coli ribonuclease (RNase) H, and RNase R. The modularity of the DNA switch template allowed\na rational design of a synthetic DNA switch regulated by its RNA output acting as a transcription activator. We verified\nthat the thermodynamic and kinetic constraints dictated by the sequence design criteria were enough to experimentally\nachieve the intended dynamics: a transcription activator configured to regulate its own production. Although only\nRNase H is necessary to achieve bistability of switch states, RNase R is necessary to maintain stable RNA signal levels and\nto control incomplete degradation products. A simple mathematical model was used to fit ensemble parameters for the\ntraining set of experimental results and was then directly applied to predict time-courses of switch dynamics and sensitivity\nto parameter variations with reasonable agreement. The positive autoregulation switches can be used to provide constant\ninput signals and store outputs of biochemical networks and are potentially useful for chemical control applications.", "date": "2011-01-05", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechAUTHORS:20111020-092905148", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-092905148", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.48550/arXiv.1101.0723", "primary_object": { "basename": "self-activating-switch2011.pdf", "url": "https://authors.library.caltech.edu/records/qrkyb-dzm06/files/self-activating-switch2011.pdf" }, "resource_type": "monograph", "pub_year": "2011", "author_list": "Subsoontorn, Pakpoom; Kim, Jongmin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/dt6t7-c2710", "eprint_id": 27111, "eprint_status": "archive", "datestamp": "2023-08-19 04:54:02", "lastmod": "2024-01-13 05:42:34", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Efficient Turing-Universal Computation with DNA Polymers", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2011 Springer-Verlag Berlin Heidelberg. \n\nWe thank Ho-Lin Chen for insightful discussions and suggestions. Our development of the history-free CRN scheme grew out of extensive discussions with Luca Cardelli. We thank Anne Condon for clarifying discussions. This work was supported by the Molecular Programming Project under NSF grant 0832824 and an NSF CIFellows Award to DS.\n\nSubmitted - DNA_stack_machines2010_DNA16.pdf
", "abstract": "Bennett's proposed chemical Turing machine is one of the most important thought experiments in the study of the thermodynamics of computation. Yet the sophistication of molecular engineering required to physically construct Bennett's hypothetical polymer substrate and enzymes has deterred experimental implementations. Here we propose a chemical implementation of stack machines \u2014 a Turing-universal model of computation similar to Turing machines \u2014 using DNA strand displacement cascades as the underlying chemical primitive. More specifically, the mechanism described herein is the addition and removal of monomers from the end of a DNA polymer, controlled by strand displacement logic. We capture the motivating feature of Bennett's scheme: that physical reversibility corresponds to logically reversible computation, and arbitrarily little energy per computation step is required. Further, as a method of embedding logic control into chemical and biological systems, polymer-based chemical computation is significantly more efficient than geometry-free chemical reaction networks.", "date": "2011", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "123-140", "id_number": "CaltechAUTHORS:20111006-081731222", "isbn": "978-3-642-18304-1", "book_title": "DNA computing and molecular programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111006-081731222", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0832824" } ] }, "contributors": { "items": [ { "id": "Sakakibara-Y", "name": { "family": "Sakakibara", "given": "Yasubumi" } }, { "id": "Mi-Y", "name": { "family": "Mi", "given": "Y." } } ] }, "doi": "10.1007/978-3-642-18305-8_12", "primary_object": { "basename": "DNA_stack_machines2010_DNA16.pdf", "url": "https://authors.library.caltech.edu/records/dt6t7-c2710/files/DNA_stack_machines2010_DNA16.pdf" }, "resource_type": "book_section", "pub_year": "2011", "author_list": "Qian, Lulu; Soloveichik, David; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/52pjb-zvg80", "eprint_id": 27411, "eprint_status": "archive", "datestamp": "2023-08-19 04:54:36", "lastmod": "2024-01-13 05:44:15", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Simple Evolution of Complex Crystal Species", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2011 Springer-Verlag Berlin Heidelberg.", "abstract": "Cairns-Smith has proposed that life began as structural patterns in clays that self-replicated during cycles of crystal growth and fragmentation. Complex, evolved crystal forms could then have catalyzed the formation of a more advanced genetic material. A crucial weakness of this theory is that it is unclear how complex crystals might arise through Darwinian selection. Here we investigate whether complex crystal patterns could evolve using a model system for crystal growth, DNA tile crystals, that is amenable to both theoretical and experimental inquiry. It was previously shown that in principle, the evolution of crystals assembled from a set of thousands of DNA tiles under very specific environmental conditions could produce arbitrarily complex patterns. Here we show that evolution driven only by the dearth of one monomer type could produce complex crystals from just 12 monomer types. The proposed mechanism of evolution is simple enough to test experimentally and is sufficiently general that it may apply to other DNA tile crystals or even to natural crystals, suggesting that complex crystals could evolve from simple starting materials because of relative differences in concentrations of the materials needed for growth.", "date": "2011", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "147-161", "id_number": "CaltechAUTHORS:20111025-131913963", "isbn": "978-3-642-18304-1", "book_title": "DNA Computing and Molecular Programming", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111025-131913963", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Sakakibara-Y", "name": { "family": "Sakakibara", "given": "Yasubumi" } }, { "id": "Mi-Y-L", "name": { "family": "Mi", "given": "Yongli L." } } ] }, "doi": "10.1007/978-3-642-18305-8_14", "resource_type": "book_section", "pub_year": "2011", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/74b6p-jfw34", "eprint_id": 18970, "eprint_status": "archive", "datestamp": "2023-08-19 02:55:44", "lastmod": "2023-10-20 19:14:53", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-D-Y", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Robustness and modularity properties of a non-covalent DNA catalytic reaction", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s) 2010. Published by Oxford University Press.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/\nby-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\n\nReceived November 18, 2009; Revised January 29, 2010; Accepted February 2, 2010.\nAdvance Access originally published online on March 1, 2010.\n\nWe thank Georg Seelig and David Soloveichik for\ninsightful discussions.\nFunding: National Science Foundation (grants 0506468, 0622254,\n0533064 and 0728703 to D.Y.Z. and E.W.) Fannie and\nJohn Hertz Foundation (to D.Y.Z.). Funding for open\naccess charge: the National Science Foundation grant\n0728703.\n\nPublished - Zhang2010p10607Nucleic_Acids_Res.pdf
", "abstract": "The biophysics of nucleic acid hybridization and strand displacement have been used for the rational design of a number of nanoscale structures and functions. Recently, molecular amplification methods have been developed in the form of non-covalent DNA catalytic reactions, in which single-stranded DNA (ssDNA) molecules catalyze the release of ssDNA product molecules from multi-stranded complexes. Here, we characterize the robustness and specificity of one such strand displacement-based catalytic reaction. We show that the designed reaction is simultaneously sensitive to sequence mutations in the catalyst and robust to a variety of impurities and molecular noise. These properties facilitate the incorporation of strand displacement-based DNA components in synthetic chemical and biological reaction networks.", "date": "2010-07", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "38", "number": "12", "publisher": "Oxford University Press", "pagerange": "4182-4197", "id_number": "CaltechAUTHORS:20100709-132352904", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100709-132352904", "rights": "This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/\nby-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0506468" }, { "agency": "NSF", "grant_number": "0622254" }, { "agency": "NSF", "grant_number": "0533064" }, { "agency": "NSF", "grant_number": "0728703" }, { "agency": "Fannie and John Hertz Foundation" } ] }, "doi": "10.1093/nar/gkq088", "primary_object": { "basename": "Zhang2010p10607Nucleic_Acids_Res.pdf", "url": "https://authors.library.caltech.edu/records/74b6p-jfw34/files/Zhang2010p10607Nucleic_Acids_Res.pdf" }, "resource_type": "article", "pub_year": "2010", "author_list": "Zhang, David Yu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5n7eg-e4d27", "eprint_id": 18532, "eprint_status": "archive", "datestamp": "2023-08-19 02:33:19", "lastmod": "2023-10-20 16:29:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lund-K", "name": { "family": "Lund", "given": "Kyle" } }, { "id": "Manzo-A-J", "name": { "family": "Manzo", "given": "Anthony J." } }, { "id": "Dabby-N", "name": { "family": "Dabby", "given": "Nadine" } }, { "id": "Michelotti-N", "name": { "family": "Michelotti", "given": "Nicole" } }, { "id": "Johnson-Buck-A", "name": { "family": "Johnson-Buck", "given": "Alexander" } }, { "id": "Nangreave-J", "name": { "family": "Nangreave", "given": "Jeanette" } }, { "id": "Taylor-S", "name": { "family": "Taylor", "given": "Steven" } }, { "id": "Pei-Renjjun", "name": { "family": "Pei", "given": "Renjun" } }, { "id": "Stojanovic-M-N", "name": { "family": "Stojanovic", "given": "Milan N." } }, { "id": "Walter-N-G", "name": { "family": "Walter", "given": "Nils G." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Yan-Hao", "name": { "family": "Yan", "given": "Hao" } } ] }, "title": "Molecular robots guided by prescriptive landscapes", "ispublished": "pub", "full_text_status": "public", "keywords": "biochemistry", "note": "\u00a9 2010 Macmillan Publishers Limited. \n\nReceived 31 March 2009. Accepted 11 March 2010. \n\nThis research was supported by the US National Science Foundation (NSF) EMT and CBC grants (all authors); fellowships and grants from the Kinship Foundation (Searle), the Leukemia & Lymphoma Society, the Juvenile Diabetes Research Foundation and NSF ITR (M.N.S.); awards from the US Army Research Office, the NSF, the US Office of Naval Research, the US National Institutes of Health, the US Department of Energy and a Sloan Research Fellowship (H.Y.); an NSF Graduate Fellowship (N.D.); and Molecular Biophysics and Microfluidics in Biomedical Sciences Training Fellowships from the NIH (A.J.-B. and N.M., respectively). M.N.S. is grateful to T. E. Mitchell and M. Olah for\ninspiration, discussions and help. \n\nAuthor Contributions: AFM experiments were performed by K.L. (majority), J.N. and N.D.; analysis was performed by N.D., K.L., J.N. and S.T. and supervised by E.W. and H.Y. Fluorescence microscopy and particle tracking analysis were performed by A.J.M., N.M. and A.J.-B, supervised by N.G.W. Spiders were synthesized and purified, and their integrity was confirmed and monitored, by S.T. Surface plasmon resonance experiments were performed by R.P. Research coordination was by M.N.S. and materials transfer coordination was by S.T., J.N. and K.L. Experimental design and manuscript preparation received input from all authors.\n\nSupplemental Material - nature09012-s1.pdf
", "abstract": "Traditional robots rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment. A first step in this direction was the development of DNA walkers, which have developed from being non-autonomous, to being capable of directed but brief motion on one-dimensional tracks. Here we demonstrate that previously developed random walkers\u2014so-called molecular spiders that comprise a streptavidin molecule as an inert 'body' and three deoxyribozymes as catalytic 'legs'\u2014show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as 'start', 'follow', 'turn' and 'stop'. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour.", "date": "2010-05-13", "date_type": "published", "publication": "Nature", "volume": "465", "number": "7295", "publisher": "Nature Publishing Group", "pagerange": "206-210", "id_number": "CaltechAUTHORS:20100602-145349454", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100602-145349454", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF" }, { "agency": "Kinship Foundation (Searle)" }, { "agency": "Leukemia & Lymphoma Society" }, { "agency": "Juvenile Diabetes Research Foundation" }, { "agency": "Army Research Office (ARO)" }, { "agency": "Office of Naval Research (ONR)" }, { "agency": "NIH Predoctoral Fellowship" }, { "agency": "Department of Energy (DOE)" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "collection": "CaltechAUTHORS", "doi": "10.1038/nature09012", "primary_object": { "basename": "nature09012-s1.pdf", "url": "https://authors.library.caltech.edu/records/5n7eg-e4d27/files/nature09012-s1.pdf" }, "resource_type": "article", "pub_year": "2010", "author_list": "Lund, Kyle; Manzo, Anthony J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/m050w-byd24", "eprint_id": 17951, "eprint_status": "archive", "datestamp": "2023-08-21 23:37:16", "lastmod": "2023-10-20 15:27:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "DNA as a universal substrate for chemical kinetics", "ispublished": "pub", "full_text_status": "public", "keywords": "molecular programming; mass-action kinetics; strand displacement cascades; chemical reaction networks; nonlinear chemical dynamics", "note": "\u00a9 2010 by the National Academy of Sciences.\n\nEdited by Jos\u00e9 N. Onuchic, University of California San Diego, La Jolla, CA, and approved January 29, 2010 (received for review August 18, 2009).\nPublished online before print March 4, 2010.\nA preliminary version of this work appeared as ref. 52.\nWe thank L. Cardelli, D. Dotty, L. Qian, D. Zhang,\nJ. Schaeffer, and M. Magnasco for useful discussions. This work was supported\nby National Science Foundation Grants EMT-0728703 and CCF-0832824 and\nHuman Frontier Science Program Award RGY0074/2006-C.D.S. D.S. was supported\nby the CIFellows project. G.S. was supported by the Swiss National\nScience Foundation and a Burroughs Wellcome Fund CASI award.\n\nAuthor contributions: D.S., G.S., and E.W. designed research, performed research,\nand wrote the paper.\n\nPublished - Soloveichik2010p7436P_Natl_Acad_Sci_Usa.pdf
Supplemental Material - pnas.0909380107_SI.pdf
", "abstract": "Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka\u2013Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior.", "date": "2010-03-23", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "107", "number": "12", "publisher": "National Academy of Sciences", "pagerange": "5393-5398", "id_number": "CaltechAUTHORS:20100413-092145583", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100413-092145583", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "EMT-0728703" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" }, { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "CASI" } ] }, "doi": "10.1073/pnas.0909380107", "pmcid": "PMC2851759", "primary_object": { "basename": "Soloveichik2010p7436P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/m050w-byd24/files/Soloveichik2010p7436P_Natl_Acad_Sci_Usa.pdf" }, "related_objects": [ { "basename": "pnas.0909380107_SI.pdf", "url": "https://authors.library.caltech.edu/records/m050w-byd24/files/pnas.0909380107_SI.pdf" } ], "resource_type": "article", "pub_year": "2010", "author_list": "Soloveichik, David; Seelig, Georg; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2j9f6-zkm23", "eprint_id": 17681, "eprint_status": "archive", "datestamp": "2023-08-19 01:16:15", "lastmod": "2023-10-20 00:08:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Maune-Hareem-T", "name": { "family": "Maune", "given": "Hareem T." } }, { "id": "Han-Si-ping", "name": { "family": "Han", "given": "Si-ping" }, "orcid": "0000-0002-2213-4953" }, { "id": "Barish-Robert-D", "name": { "family": "Barish", "given": "Robert D." } }, { "id": "Bockrath-M-W", "name": { "family": "Bockrath", "given": "Marc" } }, { "id": "Goddard-W-A-III", "name": { "family": "Goddard", "given": "William A., III" }, "orcid": "0000-0003-0097-5716" }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates", "ispublished": "pub", "full_text_status": "public", "keywords": "Carbon nanotubes and fullerenes | Molecular self-assembly", "note": "\u00a9 2010 Macmillan Publishers Limited. \n\nReceived 14 April 2009; Accepted 21 September 2009; Published online 8 November 2009. \n\nThis work was supported by the National Science Foundation (CBET/NIRT 0608889; CCF/NANO/EMT 0622254 and 0829951), the Office of Naval Research (N00014-05-1-0562) and the Center on Functional Engineered Nano Architectures (FENA, Theme 2 and Theme 3). P.W.K.R. thanks Microsoft Corporation for support. S.H. thanks Julie Norville for helpful discussions. \n\nAuthor Contributions: H.T.M., S.H. and R.D.B. conceived of the project, designed the structures, conducted the experiments and took the measurements with advice and consultation from all authors. All authors contributed to writing the paper. M.B., W.A.G., P.W.K.R. and E.W. provided financial support.\n\nSupplemental Material - nnano.2009.311-s1.pdf
", "abstract": "A central challenge in nanotechnology is the parallel fabrication of complex geometries for nanodevices. Here we report a general method for arranging single-walled carbon nanotubes in two dimensions using DNA origami\u2014a technique in which a long single strand of DNA is folded into a predetermined shape. We synthesize rectangular origami templates (~75 nm \u00d7 95 nm) that display two lines of single-stranded DNA 'hooks' in a cross pattern with ~6 nm resolution. The perpendicular lines of hooks serve as sequence-specific binding sites for two types of nanotubes, each functionalized non-covalently with a distinct DNA linker molecule. The hook-binding domain of each linker is protected to ensure efficient hybridization. When origami templates and DNA-functionalized nanotubes are mixed, strand displacement-mediated deprotection and binding aligns the nanotubes into cross-junctions. Of several cross-junctions synthesized by this method, one demonstrated stable field-effect transistor-like behaviour. In such organizations of electronic components, DNA origami serves as a programmable nanobreadboard; thus, DNA origami may allow the rapid prototyping of complex nanotube-based structures.", "date": "2010-01", "date_type": "published", "publication": "Nature Nanotechnology", "volume": "5", "number": "1", "publisher": "Nature Publishing Group", "pagerange": "61-66", "id_number": "CaltechAUTHORS:20100305-145736806", "issn": "1748-3387", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100305-145736806", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CBET-0608889" }, { "agency": "NSF", "grant_number": "CCF-0622254" }, { "agency": "NSF", "grant_number": "CCF-0829951" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-05-1-0562" }, { "agency": "Center on Functional Engineered Nano Architecture" } ] }, "collection": "CaltechAUTHORS", "doi": "10.1038/nnano.2009.311", "primary_object": { "basename": "nnano.2009.311-s1.pdf", "url": "https://authors.library.caltech.edu/records/2j9f6-zkm23/files/nnano.2009.311-s1.pdf" }, "resource_type": "article", "pub_year": "2010", "author_list": "Maune, Hareem T.; Han, Si-ping; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/a4spy-d6v98", "eprint_id": 16887, "eprint_status": "archive", "datestamp": "2023-08-19 00:47:09", "lastmod": "2023-10-19 22:38:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-D-Y", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Control of DNA Strand Displacement Kinetics Using Toehold Exchange", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2009 American Chemical Society.\n\nReceived: August 18, 2009.\nPublication Date (Web): November 6, 2009.\n\n\nWe thank Xi Chen for a very careful reading\nof this paper and useful suggestions regarding the binding energy\ncalculations. We thank Karthik Sarma for useful suggestions\nregarding rate constant fitting. We thank Niles Pierce, Justin Bois,\nand Joe Zadeh for discussion on the energetics parameters used by\nNUPACK. We thank Niles Pierce, Anne Condon, and Victor Beck\nfor many helpful suggestions in the revision of the manuscript. We\nthank Bernard Yurke, Georg Seelig, and Joseph Schaeffer for\ninsightful discussions. D.Y.Z. and E.W. were supported by NSF\ngrants 0506468, 0622254, 0533064, 0728703, and 0832824. D.Y.Z.\nis supported by the Fannie and John Hertz Foundation.\n\nSupplemental Material - ja906987s_si_001.pdf
", "abstract": "DNA is increasingly being used as the engineering material of choice for the construction of nanoscale circuits, structures, and motors. Many of these enzyme-free constructions function by DNA strand displacement reactions. The kinetics of strand displacement can be modulated by toeholds, short single-stranded segments of DNA that colocalize reactant DNA molecules. Recently, the toehold exchange process was introduced as a method for designing fast and reversible strand displacement reactions. Here, we characterize the kinetics of DNA toehold exchange and model it as a three-step process. This model is simple and quantitatively predicts the kinetics of 85 different strand displacement reactions from the DNA sequences. Furthermore, we use toehold exchange to construct a simple catalytic reaction. This work improves the understanding of the kinetics of nucleic acid reactions and will be useful in the rational design of dynamic DNA and RNA circuits and nanodevices.", "date": "2009-12-02", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "131", "number": "47", "publisher": "American Chemical Society", "pagerange": "17303-17314", "id_number": "CaltechAUTHORS:20091207-100833395", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20091207-100833395", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "0506468" }, { "agency": "NSF", "grant_number": "0622254" }, { "agency": "NSF", "grant_number": "0533064" }, { "agency": "NSF", "grant_number": "0728703" }, { "agency": "NSF", "grant_number": "0832824" }, { "agency": "Fannie and John Hertz Foundation" } ] }, "doi": "10.1021/ja906987s", "primary_object": { "basename": "ja906987s_si_001.pdf", "url": "https://authors.library.caltech.edu/records/a4spy-d6v98/files/ja906987s_si_001.pdf" }, "resource_type": "article", "pub_year": "2009", "author_list": "Zhang, David Yu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yryqp-pwa77", "eprint_id": 27329, "eprint_status": "archive", "datestamp": "2023-08-21 22:15:40", "lastmod": "2023-10-24 17:04:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fujibayashi-Kenichi", "name": { "family": "Fujibayashi", "given": "Kenichi" } }, { "id": "Zhang-David-Yu", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Murata-Satoshi", "name": { "family": "Murata", "given": "Satoshi" } } ] }, "title": "Error suppression mechanisms for DNA tile self-assembly and their simulation", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Algorithmic self-assembly; Assembly errors; Branch migration; DNA self-assembly; Protecting molecules", "note": "\u00a9 2008 Springer Science+Business Media B.V.\n\nThis work was supported by Grant-in-Aid for Scientific Research on Priority Areas\n(No. 17059001) from MEXT and Grant-in-Aid for Scientific Research (A) (No. 19200023) from JSPS to\nSM, JSPS Research Fellowships for Young Scientists (No. 05697) to KF, with additional support from NSF\nGrant (No. 0523761) to EW, and the Fannie and John Hertz Foundation to DYZ.", "abstract": "Algorithmic self-assembly using DNA-based molecular tiles has been demonstrated\nto implement molecular computation. When several different types of DNA tile self-assemble,\nthey can form large two-dimensional algorithmic patterns. Prior analysis predicted\nthat the error rates of tile assembly can be reduced by optimizing physical parameters such as\ntile concentrations and temperature. However, in exchange, the growth speed is also very low.\nTo improve the tradeoff between error rate and growth speed, we propose two novel error\nsuppression mechanisms: the Protected Tile Mechanism (PTM) and the Layered Tile\nMechanism (LTM). These utilize DNA protecting molecules to form kinetic barriers against\nspurious assembly. In order to analyze the performance of these two mechanisms, we\nintroduce the hybridization state Tile Assembly Model (hsTAM), which evaluates intra-tile\nstate changes as well as assembly state changes. Simulations using hsTAM suggest that the\nPTM and LTM improve the optimal tradeoff between error rate \u03b5 and growth speed r, from\nr \u2248 \u03b2\u03b5^(2.0) (for the conventional mechanism) to r \u2248 \u03b2\u03b5^(1.4) and r \u2248 \u03b2\u03b5^(0.7), respectively.", "date": "2009-09", "date_type": "published", "publication": "Natural Computing", "volume": "8", "number": "3", "publisher": "Springer", "pagerange": "589-612", "id_number": "CaltechAUTHORS:20111020-105328142", "issn": "1567-7818", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-105328142", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Priority Areas", "grant_number": "17059001" }, { "agency": "Japan Society for the Promotion of Science (JSPS)", "grant_number": "19200023" }, { "agency": "Japan Society for the Promotion of Science (JSPS)", "grant_number": "05697" }, { "agency": "NSF", "grant_number": "0523761" }, { "agency": "Fannie and John Hertz Foundation" } ] }, "doi": "10.1007/s11047-008-9093-9", "resource_type": "article", "pub_year": "2009", "author_list": "Fujibayashi, Kenichi; Zhang, David Yu; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pgm0a-wzh97", "eprint_id": 27327, "eprint_status": "archive", "datestamp": "2023-08-20 02:33:35", "lastmod": "2024-01-13 05:43:51", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" } ] }, "title": "Programmability of Chemical Reaction Networks", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2009 Springer-Verlag Berlin Heidelberg. \n\nThe research was supported in part by the \"Alpha Project\" at the Center for Genomic Experimentation and Computation, an NIH Center of Excellence (grant number P50 HG02370), as well as NSF Grants No. 0523761 and 0728703 to EW and NIMH Training Grant MH19138-15.", "abstract": "Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior.", "date": "2009-08-13", "date_type": "published", "publisher": "Springer-Verlag", "place_of_pub": "Berlin", "pagerange": "543-584", "id_number": "CaltechAUTHORS:20111020-103016495", "isbn": "978-3-540-88868-0", "book_title": "Algorithmic Bioprocesses", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-103016495", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P50 HG02370" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "MH19138-15" } ] }, "contributors": { "items": [ { "id": "Condon-A", "name": { "family": "Condon", "given": "Anne" } }, { "id": "Salomaa-A", "name": { "family": "Salomaa", "given": "Arto" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" } }, { "id": "Harel-D", "name": { "family": "Harel", "given": "David" } }, { "id": "Kok-J-N", "name": { "family": "Kok", "given": "Joost N." } } ] }, "doi": "10.1007/978-3-540-88869-7_27", "resource_type": "book_section", "pub_year": "2009", "author_list": "Cook, Matthew; Soloveichik, David; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/aqq41-kdh05", "eprint_id": 14513, "eprint_status": "archive", "datestamp": "2023-08-21 21:14:09", "lastmod": "2023-10-18 18:04:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Barish-R-D", "name": { "family": "Barish", "given": "Robert D." } }, { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "An information-bearing seed for nucleating algorithmic self-assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA nanotechnology; nucleation; crystal growth", "note": "\u00a9 2009 by The National Academy of Sciences of the USA. \n\nFreely available online through the PNAS open access option. \n\nEdited by David Baker, University of Washington, Seattle, WA, and approved January 7, 2009 (received for review September 4, 2008).\nThis work was supported by National Aeronautics and\nSpace Administration Astrobiology Grant NNG06GA50G and National Science\nFoundation Grants CCF-0432193, -0523761, -0622254, and -0832824; the Focus\nCenter Research Program\u2013 Center on Functional Engineered Nano Architectonics\nTheme 2; and a gift from Microsoft Research.\n\nPublished - Barish2009p2044P_Natl_Acad_Sci_Usa.pdf
Supplemental Material - SUPP1_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf
Supplemental Material - SUPP2_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf
", "abstract": "Self-assembly creates natural mineral, chemical, and biological structures of great complexity. Often, the same starting materials have the potential to form an infinite variety of distinct structures; information in a seed molecule can determine which form is grown as well as where and when. These phenomena can be exploited to program the growth of complex supramolecular structures, as demonstrated by the algorithmic self-assembly of DNA tiles. However, the lack of effective seeds has limited the reliability and yield of algorithmic crystals. Here, we present a programmable DNA origami seed that can display up to 32 distinct binding sites and demonstrate the use of seeds to nucleate three types of algorithmic crystals. In the simplest case, the starting materials are a set of tiles that can form crystalline ribbons of any width; the seed directs assembly of a chosen width with >90% yield. Increased structural diversity is obtained by using tiles that copy a binary string from layer to layer; the seed specifies the initial string and triggers growth under near-optimal conditions where the bit copying error rate is <0.2%. Increased structural complexity is achieved by using tiles that generate a binary counting pattern; the seed specifies the initial value for the counter. Self-assembly proceeds in a one-pot annealing reaction involving up to 300 DNA strands containing >17 kb of sequence information. In sum, this work demonstrates how DNA origami seeds enable the easy, high-yield, low-error-rate growth of algorithmic crystals as a route toward programmable bottom-up fabrication.", "date": "2009-04-14", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "106", "number": "15", "publisher": "National Academy of Sciences", "pagerange": "6054-6059", "id_number": "CaltechAUTHORS:20090708-083842545", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090708-083842545", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NASA", "grant_number": "NNG06GA" }, { "agency": "NSF", "grant_number": "CCF-0432193" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NSF", "grant_number": "CCF-0622254" }, { "agency": "NSF", "grant_number": "CCF-0832824" }, { "agency": "Functional Engineered Nano Architectonics (FENA)" }, { "agency": "Microsoft" } ] }, "doi": "10.1073/pnas.0808736106", "pmcid": "PMC2660060", "primary_object": { "basename": "SUPP1_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/aqq41-kdh05/files/SUPP1_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf" }, "related_objects": [ { "basename": "SUPP2_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/aqq41-kdh05/files/SUPP2_Barish2009p2044P_Natl_Acad_Sci_Usa.pdf" }, { "basename": "Barish2009p2044P_Natl_Acad_Sci_Usa.pdf", "url": "https://authors.library.caltech.edu/records/aqq41-kdh05/files/Barish2009p2044P_Natl_Acad_Sci_Usa.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Barish, Robert D.; Schulman, Rebecca; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/6ktsa-7vy83", "eprint_id": 18924, "eprint_status": "archive", "datestamp": "2023-08-20 00:20:54", "lastmod": "2024-01-12 23:41:09", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qian-Lulu", "name": { "family": "Qian", "given": "Lulu" }, "orcid": "0000-0003-4115-2409" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "A Simple DNA Gate Motif for Synthesizing Large-Scale Circuits", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2009 Springer-Verlag Berlin Heidelberg. \n\nThe authors thank Dave Zhang for discussion of the catalytic mechanism, Marc Riedel for providing example netlists from logic synthesis benchmarks, Virgil Griffith for suggesting useful techniques for DNA sequence design, Ho-Lin Chen and Shuki Bruck for suggesting the connection to relay circuits, David Soloveichik for Mathematica code for simulating chemical reaction networks, and Georg Seeling, Bernard Yurke, and everyone else for discussions and support. This work has been supported by NSF grant no. 0728703 and HFSP award no. RGY0074/2006-C.", "abstract": "The prospects of programming molecular systems to perform complex autonomous tasks has motivated research into the design of synthetic biochemical circuits. Of particular interest to us are cell-free nucleic acid systems that exploit non-covalent hybridization and strand displacement reactions to create cascades that implement digital and analog circuits. To date, circuits involving at most tens of gates have been demonstrated experimentally. Here, we propose a DNA catalytic gate architecture that appears suitable for practical synthesis of large-scale circuits involving possibly thousands of gates.", "date": "2009", "date_type": "published", "publisher": "Springer", "place_of_pub": "New York", "pagerange": "70-89", "id_number": "CaltechAUTHORS:20100707-102356969", "isbn": "978-3-642-03075-8", "book_title": "DNA computing : 14th International Meeting on DNA Computing, DNA 14, Prague, Czech Republic, June 2-9, 2008 : revised selected papers", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100707-102356969", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006-C" } ] }, "doi": "10.1007/978-3-642-03076-5", "resource_type": "book_section", "pub_year": "2009", "author_list": "Qian, Lulu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n9ee2-a1452", "eprint_id": 104933, "eprint_status": "archive", "datestamp": "2023-08-22 14:03:06", "lastmod": "2024-01-15 17:04:16", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "DNA as a Universal Substrate for Chemical Kinetics", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Formal Species; Bimolecular Reaction; Strand Displacement; Unimolecular Reaction; Mass Action Kinetic", "note": "\u00a9 2009 Springer-Verlag Berlin Heidelberg. \n\nThis work was supported by NSF Grant 0728703. GS acknowledges support from the Swiss National Science Foundation and the Burroughs Wellcome Fund. We thank D. Zhang, J. Schaeffer, and M. Magnasco for useful discussions.", "abstract": "We show that a DNA-based chemical system can be constructed such that it closely approximates the dynamic behavior of an arbitrary system of coupled chemical reactions. Using strand displacement reactions as a primitive we explicitly construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows for individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, correctly reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into chemistry. We illustrate our method on a chaotic R\u00f6ssler attractor; simulations of the attractor and of our proposed DNA-based implementation show good agreement.", "date": "2009", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "57-69", "id_number": "CaltechAUTHORS:20200812-121640271", "isbn": "978-3-642-03075-8", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200812-121640271", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "Burroughs Wellcome Fund" } ] }, "contributors": { "items": [ { "id": "Goel-A", "name": { "family": "Goel", "given": "Ashish" } }, { "id": "Simmel-F-C", "name": { "family": "Simmel", "given": "Friedrich C." } }, { "id": "Sos\u00edk-P", "name": { "family": "Sos\u00edk", "given": "Petr" } } ] }, "doi": "10.1007/978-3-642-03076-5_6", "resource_type": "book_section", "pub_year": "2009", "author_list": "Soloveichik, David; Seelig, Georg; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hg9r1-81463", "eprint_id": 18675, "eprint_status": "archive", "datestamp": "2023-08-22 14:00:14", "lastmod": "2023-10-20 16:39:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-Rebecca", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Programmable Control of Nucleation for Algorithmic Self-Assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "algorithmic self-assembly; DNA nanotechnology; nucleation theory", "note": "\u00a9 2009 Society for Industrial and Applied Mathematics. \n\nReceived by the editors January 17, 2007; accepted for publication (in revised form) October 5, 2009; published electronically December 4, 2009. A preliminary version of this paper appears in [40]. \n\nThe authors are grateful to Ho-Lin Chen, Ashish Goel, Zhen-Gang Wang, and Deborah Fygenson for helpful advice and discussions, and to Donald Cohen for advice on extending the results included here.\n\nPublished - Schulman2009p9781Siam_J_Comput.pdf
Submitted - 0607317.pdf
", "abstract": "Algorithmic self-assembly, a generalization of crystal growth processes, has been proposed as a mechanism for autonomous DNA computation and for bottom-up fabrication of complex nanostructures. A \"program\" for growing a desired structure consists of a set of molecular \"tiles\" designed to have specific binding interactions. A key challenge to making algorithmic self-assembly practical is designing tile set programs that make assembly robust to errors that occur during initiation and growth. One method for the controlled initiation of assembly, often seen in biology, is the use of a seed or catalyst molecule that reduces an otherwise large kinetic barrier to nucleation. Here we show how to program algorithmic self-assembly similarly, such that seeded assembly proceeds quickly but there is an arbitrarily large kinetic barrier to unseeded growth. We demonstrate this technique by introducing a family of tile sets for which we rigorously prove that, under the right physical conditions, linearly increasing the size of the tile set exponentially reduces the rate of spurious nucleation. Simulations of these \"zig-zag\" tile sets suggest that under plausible experimental conditions, it is possible to grow large seeded crystals in just a few hours such that less than 1 percent of crystals are spuriously nucleated. Simulation results also suggest that zig-zag tile sets could be used for detection of single DNA strands. Together with prior work showing that tile sets can be made robust to errors during properly initiated growth, this work demonstrates that growth of objects via algorithmic self-assembly can proceed both efficiently and with an arbitrarily low error rate, even in a model where local growth rules are probabilistic.", "date": "2009", "date_type": "published", "publication": "SIAM Journal on Computing", "volume": "39", "number": "4", "publisher": "Society for Industrial and Applied Mathematics", "pagerange": "1581-1616", "id_number": "CaltechAUTHORS:20100615-083346817", "issn": "0097-5397", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100615-083346817", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "NASA", "grant_number": "NNG06GA50G" } ] }, "doi": "10.1137/070680266", "primary_object": { "basename": "0607317.pdf", "url": "https://authors.library.caltech.edu/records/hg9r1-81463/files/0607317.pdf" }, "related_objects": [ { "basename": "Schulman2009p9781Siam_J_Comput.pdf", "url": "https://authors.library.caltech.edu/records/hg9r1-81463/files/Schulman2009p9781Siam_J_Comput.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1abkk-rra71", "eprint_id": 27331, "eprint_status": "archive", "datestamp": "2023-08-22 13:45:00", "lastmod": "2023-10-24 17:04:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" } ] }, "title": "Computation with finite stochastic chemical reaction networks", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Stochastic chemical kinetics; Molecular counts; Turing-universal computation; Probabilistic computation", "note": "\u00a9 2008 Springer Science+Business Media B.V. \n\nPublished online: 2 February 2008. \n\nWe thank G. Zavattaro for pointing out an error in an earlier version of this manuscript. This work is supported in part by the ''Alpha Project'' at the Center for Genomic Experimentation and Computation, an NIH Center of Excellence (Grant No. P50 HG02370), as well as NSF Grant No. 0523761 and NIMH Training Grant MH19138-15.", "abstract": "A highly desired part of the synthetic biology toolbox is an embedded chemical microcontroller, capable of autonomously following a logic program specified by a set of instructions, and interacting with its cellular environment. Strategies for incorporating logic in aqueous chemistry have focused primarily on implementing components, such as logic gates, that are composed into larger circuits, with each logic gate in the circuit corresponding to one or more molecular species. With this paradigm, designing and producing new molecular species is necessary to perform larger computations. An alternative approach begins by noticing that chemical systems on the small scale are fundamentally discrete and stochastic. In particular, the exact molecular counts of each molecular species present, is an intrinsically available form of information. This might appear to be a very weak form of information, perhaps quite difficult for computations to utilize. Indeed, it has been shown that error-free Turing universal computation is impossible in this setting. Nevertheless, we show a design of a chemical computer that achieves fast and reliable Turing-universal computation using molecular counts. Our scheme uses only a small number of different molecular species to do computation of arbitrary complexity. The total probability of error of the computation can be made arbitrarily small (but not zero) by adjusting the initial molecular counts of certain species. While physical implementations would be difficult, these results demonstrate that molecular counts can be a useful form of information for small molecular systems such as those operating within cellular environments.", "date": "2008-12", "date_type": "published", "publication": "Natural Computing", "volume": "7", "number": "4", "publisher": "Springer", "pagerange": "615-633", "id_number": "CaltechAUTHORS:20111020-132840264", "issn": "1567-7818", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-132840264", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P50 HG02370" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "MH19138-15" } ] }, "doi": "10.1007/s11047-008-9067-y", "resource_type": "article", "pub_year": "2008", "author_list": "Soloveichik, David; Cook, Matthew; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7w85s-mcj45", "eprint_id": 13360, "eprint_status": "archive", "datestamp": "2023-08-22 13:24:58", "lastmod": "2023-10-17 23:29:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-D-Y", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Dynamic allosteric control of noncovalent DNA catalysis reactions", "ispublished": "pub", "full_text_status": "restricted", "keywords": "gene-expression; rational design; RNA; ribozymes; molecules; switches; kinetics", "note": "\u00a9 2008 American Chemical Society.\nReceived May 5, 2008.\nThe authors were supported by NSF grants\n062254 and 0728703 to E.W. D.Y.Z. is supported by the Fannie\nand John Hertz Foundation.", "abstract": "Allosteric modulation of catalysis kinetics is prevalent in proteins and has been rationally designed for ribozymes. Here, we present an allosteric DNA molecule that, in its active configuration, catalyzes a noncovalent DNA reaction. The catalytic activity is designed to be modulated by the relative concentrations of two DNA regulator molecules, one an inhibitor and the other an activator. Dynamic control of the catalysis rate is experimentally demonstrated via three cycles of up and down regulation by a factor of over 10. Unlike previous works, both the allosteric receptor and catalytic core are designed, rather than evolved. This allows flexibility in the sequence design and modularity in synthetic network construction.", "date": "2008-10-22", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "130", "number": "42", "publisher": "American Chemical Society", "pagerange": "13921-13926", "id_number": "CaltechAUTHORS:ZHAjacs08", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:ZHAjacs08", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "062254" }, { "agency": "NSF", "grant_number": "0728703" }, { "agency": "Fannie and John Hertz Foundation" } ] }, "doi": "10.1021/ja803318t", "resource_type": "article", "pub_year": "2008", "author_list": "Zhang, David Yu and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gf8h4-ta232", "eprint_id": 26121, "eprint_status": "archive", "datestamp": "2023-08-19 23:39:34", "lastmod": "2023-10-24 16:14:45", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" } ] }, "title": "Programmability of Chemical Reaction Networks", "ispublished": "unpub", "full_text_status": "public", "note": "The research was supported in part by the \"Alpha Project\" at the Center for Genomic Experimentation and Computation, an NIH Center of Excellence (grant number P50 HG02370), as well as NSF Grants No. 0523761 and 0728703 to EW and NIMH Training Grant MH19138-15.\n\nSubmitted - etr090.pdf
", "abstract": "Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri Nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior.", "date": "2008-09-23", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechPARADISE:2008.ETR090", "official_url": "https://resolver.caltech.edu/CaltechPARADISE:2008.ETR090", "rights": "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P50 HG02370" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NSF", "grant_number": "CCF-0728703" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "MH19138-15" } ] }, "local_group": { "items": [ { "id": "Parallel-and-Distributed-Systems-Group" } ] }, "primary_object": { "basename": "etr090.pdf", "url": "https://authors.library.caltech.edu/records/gf8h4-ta232/files/etr090.pdf" }, "resource_type": "monograph", "pub_year": "2008", "author_list": "Cook, Matthew; Soloveichik, David; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1n480-6jz86", "eprint_id": 22739, "eprint_status": "archive", "datestamp": "2023-08-19 23:00:25", "lastmod": "2023-10-23 17:10:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fujibayashi-K", "name": { "family": "Fujibayashi", "given": "Kenichi" } }, { "id": "Hariadi-R", "name": { "family": "Hariadi", "given": "Rizal" } }, { "id": "Park-S-H", "name": { "family": "Park", "given": "Sung Ha" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Murata-S", "name": { "family": "Murata", "given": "Satoshi" } } ] }, "title": "Toward reliable algorithmic self-assembly of DNA tiles: A fixed-width cellular automaton pattern", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2008 American Chemical Society.\n\nReceived September 7, 2007; Revised Manuscript Received October 10, 2007.\nPublication Date (Web): December 28, 2007.\nThis work was supported by Grant-in-Aid for Scientific Research on Priority Areas (No. 17059001)\nfrom MEXT and Grant-in-Aid for Scientific Research (A) (No.\n19200023) from JSPS to S.M., JSPS Research Fellowships for\nYoung Scientists (No. 05697) to K.F., with additional support\nfrom NSF Grants (Nos. 0432193, 0093486) to E.W., and a\nCenter for the Physics of Information postdoctoral fellowship\nto S.H.P.\n\nSupplemental Material - sierpinski_ribbons_supp_1_.pdf
", "abstract": "Bottom-up fabrication of nanoscale structures relies on chemical processes to direct self-assembly. The complexity, precision, and yield achievable by a one-pot reaction are limited by our ability to encode assembly instructions into the molecules themselves. Nucleic acids provide a platform for investigating these issues, as molecular structure and intramolecular interactions can encode growth rules. Here, we use DNA tiles and DNA origami to grow crystals containing a cellular automaton pattern. In a one-pot annealing reaction, 250 DNA strands first assemble into a set of 10 free tile types and a seed structure, then the free tiles grow algorithmically from the seed according to the automaton rules. In our experiments, crystals grew to ~300 nm long, containing ~300 tiles with an initial assembly error rate of ~1.4% per tile. This work provides evidence that programmable molecular self-assembly may be sufficient to create a wide range of complex objects in one-pot reactions.", "date": "2008-07", "date_type": "published", "publication": "Nano Letters", "volume": "8", "number": "7", "publisher": "American Chemical Society", "pagerange": "1791-1797", "id_number": "CaltechAUTHORS:20110309-104158035", "issn": "1530-6984", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104158035", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Priority Areas", "grant_number": "17059001" }, { "agency": "Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research", "grant_number": "19200023" }, { "agency": "Japan Society for the Promotion of Science (JSPS) Research Fellowships Young Scientists", "grant_number": "05697" }, { "agency": "NSF", "grant_number": "0432193" }, { "agency": "NSF", "grant_number": "0093486" }, { "agency": "Center for the Physics of Information Postdoctoral Fellowship" } ] }, "doi": "10.1021/nl0722830", "primary_object": { "basename": "sierpinski_ribbons_supp_1_.pdf", "url": "https://authors.library.caltech.edu/records/1n480-6jz86/files/sierpinski_ribbons_supp_1_.pdf" }, "resource_type": "article", "pub_year": "2008", "author_list": "Fujibayashi, Kenichi; Hariadi, Rizal; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7gj5t-g0873", "eprint_id": 27334, "eprint_status": "archive", "datestamp": "2023-08-22 11:53:36", "lastmod": "2023-10-24 17:04:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Combining self-healing and proofreading in self-assembly", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA nanotechnology; Error-correction; Proofreading; Self-assembly; Self-healing; Tile Assembly Model", "note": "\u00a9 2007 Springer Science+Business Media B.V. \n\nReceived: 1 September 2006; Accepted: 19 February 2007; Published online: 6 April 2007. \n\nWe thank Ho-Lin Chen and Ashish Goel for insightful conversations and suggestions. \n\nThis work was supported by NSF Grant No. 0523761.\n\nSubmitted - selfhealing_proofreading_preprint_1_.pdf
", "abstract": "Molecular self-assembly is a promising approach to bottom-up fabrication of complex structures. A major impediment to the practical use of self-assembly to create complex structures is the high rate of error under existing experimental conditions. Recent theoretical work on algorithmic self-assembly has shown that under a realistic model of tile addition and detachment, error correcting tile sets are possible that can recover from the attachment of incorrect tiles during the assembly process. An orthogonal type of error correction was recently considered as well: whether damage to a completed structure can be repaired. It was shown that such self-healing tile sets are possible. However, these tile sets are not robust to the incorporation of incorrect tiles. It remained an open question whether it is possible to create tile sets that can simultaneously resist wholesale removal of tiles and the incorporation of incorrect ones. Here we present a method for converting a tile set producing a pattern on the quarter plane into a tile set that makes the same pattern (at a larger scale) but is able to withstand both of these types of errors.", "date": "2008-06", "date_type": "published", "publication": "Natural Computing", "volume": "7", "number": "2", "publisher": "Springer", "pagerange": "203-218", "id_number": "CaltechAUTHORS:20111020-141746718", "issn": "1567-7818", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-141746718", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0523761" } ] }, "doi": "10.1007/s11047-007-9036-x", "primary_object": { "basename": "selfhealing_proofreading_preprint_1_.pdf", "url": "https://authors.library.caltech.edu/records/7gj5t-g0873/files/selfhealing_proofreading_preprint_1_.pdf" }, "resource_type": "article", "pub_year": "2008", "author_list": "Soloveichik, David; Cook, Matthew; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hxxek-42p61", "eprint_id": 27333, "eprint_status": "archive", "datestamp": "2023-08-22 11:53:27", "lastmod": "2023-10-24 17:04:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "How crystals that sense and respond to their environments could evolve", "ispublished": "pub", "full_text_status": "public", "keywords": "Evolution; Complexity; Universality; Crystals; Self-assembly; Tiles; Metabolism", "note": "\u00a9 2007 Springer Science+Business Media B.V. \nReceived: 1 September 2006; Accepted: 26 March 2007; Published online: 13 June 2007.\nWe thank Andrew Turberfield, Paul Rothemund, Robert Barish, Ho-Lin Chen, and Ashish Goel for insightful conversations and suggestions. This work was supported by NASA Grant No.\nNNG06GA50G.\n\nSubmitted - metabolism_preprint_1_.pdf
", "abstract": "An enduring mystery in biology is how a physical entity simple enough to have arisen spontaneously could have evolved into the complex life seen on Earth today. Cairns-Smith has proposed that life might have originated in clays which stored genomes consisting of an arrangement of crystal monomers that was replicated during growth. While a clay genome is simple enough to have conceivably arisen spontaneously, it is not obvious how it might have produced more complex forms as a result of evolution. Here, we examine this possibility in the tile assembly model, a generalized model of crystal growth that has been used to study the self-assembly of DNA tiles. We describe hypothetical crystals for which evolution of complex crystal sequences is driven by the scarceness of resources required for growth. We show how, under certain circumstances, crystal growth that performs computation can predict which resources are abundant. In such cases, crystals executing programs that make these predictions most accurately will grow fastest. Since crystals can perform universal computation, the complexity of computation that can be used to optimize growth is unbounded. To the extent that lessons derived from the tile assembly model might be applicable to mineral crystals, our results suggest that resource scarcity could conceivably have provided the evolutionary pressures necessary to produce complex clay genomes that sense and respond to changes in their environment.", "date": "2008-06", "date_type": "published", "publication": "Natural Computing", "volume": "7", "number": "2", "publisher": "Springer", "pagerange": "219-237", "id_number": "CaltechAUTHORS:20111020-140158137", "issn": "1567-7818", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-140158137", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NASA", "grant_number": "NNG06GA50G" } ] }, "doi": "10.1007/s11047-007-9046-8", "primary_object": { "basename": "metabolism_preprint_1_.pdf", "url": "https://authors.library.caltech.edu/records/hxxek-42p61/files/metabolism_preprint_1_.pdf" }, "resource_type": "article", "pub_year": "2008", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2n7w7-0kb24", "eprint_id": 73272, "eprint_status": "archive", "datestamp": "2023-08-19 22:17:53", "lastmod": "2023-10-24 15:11:07", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Toward molecular programming with DNA", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2008 ACM.\n\nPresentation - 1346282.mp3
Presentation - 1346282.mp4
Presentation - p1-erik-slides.zip
", "abstract": "Biological organisms are beautiful examples of programming. The program and data are stored in biological molecules such as DNA, RNA, and proteins; the algorithms are carried out by molecular and biochemical processes; and the end result is the creation and function of an organism. If we understood how to program molecular systems, what could we create? Lifelike technologies whose basic operations are chemical reactions? The fields of chemistry, physics, biology, and computer science are converging as we begin to synthesize molecules, molecular machines, and molecular systems of ever increasing complexity, leading to subdisciplines such as DNA nanotechnology, DNA computing, and synthetic biology. Having demonstrated simple devices and systems -- self-assembled structures, molecular motors, chemical logic gates -- researchers are now turning to the question of how to create large-scale integrated systems. To do so, we must learn how to manage complexity: how to efficiently specify the structure and behavior of intricate molecular systems, how to compile such specifications down to the design of molecules to be synthesized in the lab, and how to ensure that such systems function robustly. These issues will be illustrated for chemical logic circuits based on cascades of DNA hybridization reactions.", "date": "2008-03", "date_type": "published", "publisher": "ACM", "place_of_pub": "New York, NY", "id_number": "CaltechAUTHORS:20170105-124404623", "isbn": "978-1-59593-958-6", "book_title": "ASPLOS XIII Proceedings of the 13th international conference on Architectural support for programming languages and operating systems", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170105-124404623", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Eggers-S", "name": { "family": "Eggers", "given": "Susan" } } ] }, "doi": "10.1145/1346281.1346282", "primary_object": { "basename": "1346282.mp3", "url": "https://authors.library.caltech.edu/records/2n7w7-0kb24/files/1346282.mp3" }, "related_objects": [ { "basename": "1346282.mp4", "url": "https://authors.library.caltech.edu/records/2n7w7-0kb24/files/1346282.mp4" }, { "basename": "p1-erik-slides.zip", "url": "https://authors.library.caltech.edu/records/2n7w7-0kb24/files/p1-erik-slides.zip" } ], "resource_type": "book_section", "pub_year": "2008", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/mnqg5-fnw89", "eprint_id": 22746, "eprint_status": "archive", "datestamp": "2023-08-19 21:29:21", "lastmod": "2023-10-23 17:10:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-David-Yu", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Turberfield-A-J", "name": { "family": "Turberfield", "given": "Andrew J." } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Engineering entropy-driven reactions and networks catalyzed by DNA", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Association for the Advancement of Science. \nReceived for publication 30 July 2007. \nAccepted for publication 8 October 2007.\nWe thank X. R. Bao, G. Seelig, D. Soloveichik,\nP. Rothemund, and L. Adleman for insightful\ndiscussions. There is a patent pending on this work.\nD.Y.Z. and A.J.T. were supported by UK research\ncouncils (Engineering and Physical Sciences Research\nCouncil, Biotechnology and Biological Sciences Research\nCouncil, Medical Research Council, and the Ministry of\nDefense) though the Bionanotechnology Interdisciplinary\nResearch Collaboration. D.Y.Z. and E.W. were supported\nby a Caltech Grubstake Grant and NSF grants 0506468,\n0622254, and 0533064. D.Y.Z. is supported by the\nFannie and John Hertz Foundation.\n\nSupplemental Material - Zhang.SOM_1_.pdf
", "abstract": "Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the\n engineering of electromechanical devices. Toward that end, nucleic\n acids provide a designable substrate for the regulation of biochemical\n reactions. However, it has been difficult to incorporate signal\n amplification components. We introduce a design strategy that allows a\n specified input oligonucleotide to catalyze the release of a specified\n output oligonucleotide, which in turn can serve as a catalyst for other\n reactions. This reaction, which is driven forward by the\n configurational entropy of the released molecule, provides an\n amplifying circuit element that is simple, fast, modular, composable,\n and robust. We have constructed and characterized several circuits that\n amplify nucleic acid signals, including a feedforward cascade with\n quadratic kinetics and a positive feedback circuit with exponential\n growth kinetics.", "date": "2007-11-16", "date_type": "published", "publication": "Science", "volume": "318", "number": "5853", "publisher": "American Association for the Advancement of Science", "pagerange": "1121-1125", "id_number": "CaltechAUTHORS:20110309-104159433", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104159433", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Engineering and Physical Sciences Research Council (EPSRC)" }, { "agency": "Biotechnology and Biological Sciences Research Council (BBSRC)" }, { "agency": "Medical Research Council (UK)" }, { "agency": "Ministry of Defense (UK)" }, { "agency": "Bionanotechnology Interdisciplinary Research Collaboration" }, { "agency": "Caltech Grubstake Grant" }, { "agency": "NSF", "grant_number": "DMS-0506468" }, { "agency": "NSF", "grant_number": "CCF-0622254" }, { "agency": "NSF", "grant_number": "CHE-0533064" }, { "agency": "Fannie and John Hertz Foundation" } ] }, "doi": "10.1126/science.1148532", "primary_object": { "basename": "Zhang.SOM_1_.pdf", "url": "https://authors.library.caltech.edu/records/mnqg5-fnw89/files/Zhang.SOM_1_.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Zhang, David Yu; Turberfield, Andrew J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jm01n-vjr56", "eprint_id": 8837, "eprint_status": "archive", "datestamp": "2023-08-22 10:05:15", "lastmod": "2023-10-16 21:45:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Synthesis of crystals with a programmable kinetic barrier to nucleation", "ispublished": "pub", "full_text_status": "public", "keywords": "algorithmic self-assembly, DNA nanotechnology, self-assembly, supramolecular chemistry", "note": "\u00a9 2007 by the National Academy of Sciences. \n\nEdited by Alan R. Fersht, University of Cambridge, Cambridge, United Kingdom, and approved July 19, 2007 (received for review February 16, 2007). Published online before print September 19, 2007.\n\nWe thank Paul Rothemund, Bernie Yurke, Peng Yin, Ho-Lin Chen, Rizal Hariadi, Rick Flagan, and Rob Barish for insightful discussions and encouragement. This work was supported by National Aeronautics and Space Administration Astrobiology Grant NNG06GA50G and National Science Foundation Grant NANO/CCF-0432193. \n\nAuthor contributions: R.S. and E.W. designed research; R.S. performed research; R.S. and E.W. analyzed data; and R.S. and E.W. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nFreely available online through the PNAS open access option. \n\nThis article contains supporting information online at www.pnas.org/cgi/content/full/0701467104/DC1.\n\nPublished - SCHUpnas07.pdf
Supplemental Material - SCHUpnas07suppinfo.pdf
", "abstract": "A central goal of chemistry is to fabricate supramolecular structures of defined function and composition. In biology, control of supramolecular synthesis is often achieved through precise control over nucleation and growth processes: A seed molecule initiates growth of a structure, but this growth is kinetically inhibited in the seed's absence. Here we show how such control can be systematically designed into self-assembling structures made of DNA tiles. These structures, \"zig-zag ribbons,\" are designed to have a fixed width but can grow arbitrarily long. Under slightly supersaturated conditions, theory predicts that elongation is always favorable but that nucleation rates decrease exponentially with increasing width. We confirm experimentally that although ribbons of different widths have similar thermodynamics, nucleation rates decrease for wider ribbons. It is therefore possible to program the nucleation rate by choosing a ribbon width. The presence of a seed molecule, a stabilized version of the presumed critical nucleus, removes the kinetic barrier to nucleation of a ribbon. Thus, we demonstrate the ability to grow supramolecular structures from rationally designed seeds, while suppressing spurious nucleation. Control over DNA tile nucleation allows for proper initiation of algorithmic crystal growth, which could lead to the high-yield synthesis of micrometer-scale structures with complex programmed features. More generally, this work shows how a self-assembly subroutine can be initiated.", "date": "2007-09-25", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "104", "number": "39", "publisher": "National Academy of Sciences", "pagerange": "15236-15241", "id_number": "CaltechAUTHORS:SCHUpnas07", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:SCHUpnas07", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NASA", "grant_number": "NNG06GA50G" }, { "agency": "NSF", "grant_number": "CCF-0432193" } ] }, "doi": "10.1073/pnas.0701467104", "pmcid": "PMC1986573", "primary_object": { "basename": "SCHUpnas07.pdf", "url": "https://authors.library.caltech.edu/records/jm01n-vjr56/files/SCHUpnas07.pdf" }, "related_objects": [ { "basename": "SCHUpnas07suppinfo.pdf", "url": "https://authors.library.caltech.edu/records/jm01n-vjr56/files/SCHUpnas07suppinfo.pdf" } ], "resource_type": "article", "pub_year": "2007", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f308m-93262", "eprint_id": 26115, "eprint_status": "archive", "datestamp": "2023-08-22 10:53:26", "lastmod": "2023-10-23 17:16:41", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bruck-J", "name": { "family": "Bruck", "given": "Jehoshua" }, "orcid": "0000-0001-8474-0812" } ] }, "title": "Computation with Finite Stochastic Chemical Reaction Networks", "ispublished": "unpub", "full_text_status": "public", "keywords": "stochastic chemical kinetics; molecular counts; Turing-universal computation; probabilistic computation", "note": "We thank G. Zavattaro for pointing out an error in an earlier version of this manuscript. This work is supported in part by the \"Alpha Project\" at the Center for Genomic Experimentation and Computation, an NIH Center of Excellence (grant no. P50 HG02370), as well as NSF Grant No. 0523761 and NIMH Training Grant MH19138-15. \n\n(Original version: September, 2007)\n\nPublished as: \n\nDavid Soloveichik, Matthew Cook, Erik Winfree, and Jehoshua Bruck (2008) Computation with finite stochastic chemical reaction networks. Natural Computing DOI: 10.1007/s11047-008-9067-y\n\nUpdated - etr085v2.pdf
", "abstract": "A highly desired part of the synthetic biology toolbox is an embedded chemical microcontroller, capable of autonomously following a logic program specified by a set of instructions, and interacting with its cellular environment. Strategies for incorporating logic in aqueous chemistry have focused primarily on implementing components, such as logic gates, that are composed into larger circuits, with each logic gate in the circuit corresponding to one or more molecular species. With this paradigm, designing and producing new molecular species is necessary to perform larger computations. An alternative approach begins by noticing that chemical systems on the small scale are fundamentally discrete and stochastic. In particular, the exact molecular counts of each molecular species present, is an intrinsically available form of information. This might appear to be a very weak form of information, perhaps quite difficult for computations to utilize. Indeed, it has been shown that error-free Turing universal computation is impossible in this setting. Nevertheless, we show a design of a chemical computer that achieves fast and reliable Turing-universal computation using molecular counts. Our scheme uses only a small number of different molecular species to do computation of arbitrary complexity. The total probability of error of the computation can be made arbitrarily small (but not zero) by adjusting the initial molecular counts of certain species. While physical implementations would be difficult, these results demonstrate that molecular counts can be a useful form of information for small molecular systems such as those operating within cellular environments.", "date": "2007-09-19", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechPARADISE:2007.ETR085", "official_url": "https://resolver.caltech.edu/CaltechPARADISE:2007.ETR085", "rights": "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P50 HG02370" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "MH19138-15" } ] }, "local_group": { "items": [ { "id": "Parallel-and-Distributed-Systems-Group" } ] }, "primary_object": { "basename": "etr085v2.pdf", "url": "https://authors.library.caltech.edu/records/f308m-93262/files/etr085v2.pdf" }, "resource_type": "monograph", "pub_year": "2007", "author_list": "Soloveichik, David; Cook, Matthew; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xgpm7-ryz35", "eprint_id": 22748, "eprint_status": "archive", "datestamp": "2023-08-19 20:51:37", "lastmod": "2023-10-23 17:10:29", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Ho-Lin", "name": { "family": "Chen", "given": "Ho-Lin" } }, { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Goel-Ashish", "name": { "family": "Goel", "given": "Ashish" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Reducing facet nucleation during algorithmic self-assembly", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Chemical Society. \n\nReceived April 4, 2007; Revised Manuscript Received July 3, 2007.\nPublication Date (Web): August 24, 2007. \n\nWe thank Paul Rothemund and an anonymous referee for useful comments and discussions. E.W. acknowledges National Science Foundation (NSF) awards 0093486 and 0432193. E.W. and A.G. acknowledge NSF award 0523761. A.G. acknowledges NSF awards 0339262 and 0323766.\n\nSupplemental Material - nl070793osi20070703_032522.pdf
", "abstract": "Algorithmic self-assembly, a generalization of crystal growth, has been proposed as a mechanism for bottom-up fabrication of complex\nnanostructures and autonomous DNA computation. In principle, growth can be programmed by designing a set of molecular tiles with binding\ninteractions that enforce assembly rules. In practice, however, errors during assembly cause undesired products, drastically reducing yields.\nHere we provide experimental evidence that assembly can be made more robust to errors by adding redundant tiles that \"proofread\" assembly.\nWe construct DNA tile sets for two methods, uniform and snaked proofreading. While both tile sets are predicted to reduce errors during\ngrowth, the snaked proofreading tile set is also designed to reduce nucleation errors on crystal facets. Using atomic force microscopy to\nimage growth of proofreading tiles on ribbon-like crystals presenting long facets, we show that under the physical conditions we studied the\nrate of facet nucleation is 4-fold smaller for snaked proofreading tile sets than for uniform proofreading tile sets.", "date": "2007-09", "date_type": "published", "publication": "Nano Letters", "volume": "7", "number": "9", "publisher": "American Chemical Society", "pagerange": "2913-2919", "id_number": "CaltechAUTHORS:20110309-104159746", "issn": "1530-6984", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104159746", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0093486" }, { "agency": "NSF", "grant_number": "CCF-0432193" }, { "agency": "NSF", "grant_number": "CCF-0523761" }, { "agency": "NSF", "grant_number": "CCF-0339262" }, { "agency": "NSF", "grant_number": "CCF-0323766" } ] }, "doi": "10.1021/nl070793o", "primary_object": { "basename": "nl070793osi20070703_032522.pdf", "url": "https://authors.library.caltech.edu/records/xgpm7-ryz35/files/nl070793osi20070703_032522.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Chen, Ho-Lin; Schulman, Rebecca; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/nmff2-tmc40", "eprint_id": 22254, "eprint_status": "archive", "datestamp": "2023-08-22 09:34:44", "lastmod": "2023-10-23 15:51:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Venkataraman-S", "name": { "family": "Venkataraman", "given": "Suvir" } }, { "id": "Dirks-R-M", "name": { "family": "Dirks", "given": "Robert M." } }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "An autonomous polymerization motor powered by DNA hybridization", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Molecular machines and motors; Nanobiotechnology", "note": "\u00a9 2007 Nature Publishing Group. \n\nReceived 14 March 2007; accepted 27 June 2007; published 29 July 2007. \n\nWe thank J. S. Bois for helpful discussions, J. Padilla for performing the early sequence design calculations,\nJ. N. Zadeh for the use of unpublished multi-objective sequence design software, J. M. Schaeffer for the use\nof unpublished multi-stranded kinetics simulation software and R. Barish and R. Hariadi for guidance on\nthe use of DNA origamis for patterning polymerization reactions. This work was funded by NSF-CCF-CAREER-0448835, NSF-CHE-0533064 (Center for Molecular Cybernetics), NSF-CCF-0622254, NSF-DMS-0506468.", "abstract": "We present a synthetic molecular motor capable of autonomous nanoscale transport in solution. Inspired by bacterial pathogens such as Rickettsia rickettsii, which locomote by inducing the polymerization of the protein actin at their surfaces to form 'comet tails', the motor operates by polymerizing a double-helical DNA tail. DNA strands are propelled processively at the living end of the growing polymers, demonstrating autonomous locomotion powered by the free energy of DNA hybridization.", "date": "2007-07-29", "date_type": "published", "publication": "Nature Nanotechnology", "volume": "2", "number": "8", "publisher": "Nature Publishing Group", "pagerange": "490-494", "id_number": "CaltechAUTHORS:20110216-154211699", "issn": "1748-3387", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110216-154211699", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0448835" }, { "agency": "NSF", "grant_number": "CHE-0533064" }, { "agency": "NSF", "grant_number": "CCF-0622254" }, { "agency": "NSF", "grant_number": "DMS-0506468" } ] }, "doi": "10.1038/nnano.2007.225", "resource_type": "article", "pub_year": "2007", "author_list": "Venkataraman, Suvir; Dirks, Robert M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1ykym-b5q43", "eprint_id": 8371, "eprint_status": "archive", "datestamp": "2023-08-22 08:26:41", "lastmod": "2023-10-16 21:27:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-David", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Complexity of Self-Assembled Shapes", "ispublished": "pub", "full_text_status": "public", "keywords": "Kolmogorov complexity; scaled shapes; self-assembly; Wang tiles; universal constructor", "note": "\u00a9 2007 Society for Industrial and Applied Mathematics. \n\nReceived December 21, 2004; accepted June 30, 2006; published February 9, 2007. \n\nWe thank Len Adleman, members of his group, Ashish Goel, and Paul Rothemund for fruitful discussions and suggestions. We also thank Rebecca Schulman and David Zhang for useful and entertaining conversations about descriptional complexity of tile systems, and an anonymous reviewer for a very careful reading of this paper and helpful comments. \n\nAn extended abstract version of this work was previously published as Complexity of self-assembled shapes, in DNA Computing, Lecture Notes in Comput. Sci. 3384, Springer, Berlin, 2005, pp. 344\u2013354. This work was supported by NSF CAREER grant 0093486.\n\nPublished - SOLsiamjc07.pdf
Submitted - 0412096.pdf
", "abstract": "The connection between self-assembly and computation suggests that a shape can be considered the output of a self-assembly \"program,\" a set of tiles that fit together to create a shape. It seems plausible that the size of the smallest self-assembly program that builds a shape and the shape's descriptional (Kolmogorov) complexity should be related. We show that when using a notion of a shape that is independent of scale, this is indeed so: in the tile assembly model, the minimal number of distinct tile types necessary to self-assemble a shape, at some scale, can be bounded both above and below in terms of the shape's Kolmogorov complexity. As part of the proof, we develop a universal constructor for this model of self-assembly that can execute an arbitrary Turing machine program specifying how to grow a shape. Our result implies, somewhat counterintuitively, that self-assembly of a scaled-up version of a shape often requires fewer tile types. Furthermore, the independence of scale in self-assembly theory appears to play the same crucial role as the independence of running time in the theory of computability. This leads to an elegant formulation of languages of shapes generated by self-assembly. Considering functions from bit strings to shapes, we show that the running-time complexity, with respect to Turing machines, is polynomially equivalent to the scale complexity of the same function implemented via self-assembly by a finite set of tile types. Our results also hold for shapes defined by Wang tiling\u2014where there is no sense of a self-assembly process\u2014except that here time complexity must be measured with respect to nondeterministic Turing machines.", "date": "2007-02-09", "date_type": "published", "publication": "SIAM Journal on Computing", "volume": "36", "number": "6", "publisher": "Society of Industrial and Applied Mathematics", "pagerange": "1544-1569", "id_number": "CaltechAUTHORS:SOLsiamjc07", "issn": "0097-5397", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:SOLsiamjc07", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" } ] }, "doi": "10.1137/S0097539704446712", "primary_object": { "basename": "0412096.pdf", "url": "https://authors.library.caltech.edu/records/1ykym-b5q43/files/0412096.pdf" }, "related_objects": [ { "basename": "SOLsiamjc07.pdf", "url": "https://authors.library.caltech.edu/records/1ykym-b5q43/files/SOLsiamjc07.pdf" } ], "resource_type": "article", "pub_year": "2007", "author_list": "Soloveichik, David and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p98fy-fvv11", "eprint_id": 7706, "eprint_status": "archive", "datestamp": "2023-08-22 08:12:37", "lastmod": "2023-10-16 21:03:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dirks-R-M", "name": { "family": "Dirks", "given": "Robert M." } }, { "id": "Bois-J-S", "name": { "family": "Bois", "given": "Justin S." }, "orcid": "0000-0001-7137-8746" }, { "id": "Schaeffer-J-M", "name": { "family": "Schaeffer", "given": "Joseph M." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Thermodynamic Analysis of Interacting Nucleic Acid Strands", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA; RNA; equilibrium; base pair; secondary structure; partition function; minimum free energy; multiple strands; dynamic programming; redundancy; distinguishability; symmetry; overcounting; dilute solution; convexity; duality", "note": "\u00a9 2007 Society for Industrial and Applied Mathematics. \n\nReceived by the editors January 27, 2006; accepted for publication (in revised form) March 30, 2006; published electronically January 30, 2007. \n\nThe first and second authors contributed equally to this work. This work was supported by grants NSF-CNS-PECASE-0093486, NSF-EIA-0113443, NSF-DMS-0506468 (IMAG), NSF-ACI-0204932, and NSF-CCF-CAREER-0448835, the Charles Lee Powell Foundation, and the Ralph M. Parsons Foundation. \n\nWe wish to thank Z.-G. Wang, M. Cook, and L.B. Pierce for helpful discussions during the course of the work.\n\nPublished - DIRsiamrev07.pdf
", "abstract": "Motivated by the analysis of natural and engineered DNA and RNA systems, we present the first algorithm for calculating the partition function of an unpseudoknotted complex of multiple interacting nucleic acid strands. This dynamic program is based on a rigorous extension of secondary structure models to the multistranded case, addressing representation and distinguishability issues that do not arise for single-stranded structures. We then derive the form of the partition function for a fixed volume containing a dilute solution of nucleic acid complexes. This expression can be evaluated explicitly for small numbers of strands, allowing the calculation of the equilibrium population distribution for each species of complex. Alternatively, for large systems (e.g., a test tube), we show that the unique complex concentrations corresponding to thermodynamic equilibrium can be obtained by solving a convex programming problem. Partition function and concentration information can then be used to calculate equilibrium base-pairing observables. The underlying physics and mathematical formulation of these problems lead to an interesting blend of approaches, including ideas from graph theory, group theory, dynamic programming, combinatorics, convex optimization, and Lagrange duality.", "date": "2007-01-30", "date_type": "published", "publication": "SIAM Review", "volume": "49", "number": "1", "publisher": "Society for Industrial and Applied Mathematics", "pagerange": "65-88", "id_number": "CaltechAUTHORS:DIRsiamrev07", "issn": "0036-1445", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:DIRsiamrev07", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "NSF", "grant_number": "EIA-0113443" }, { "agency": "NSF", "grant_number": "DMS-0506468" }, { "agency": "NSF", "grant_number": "ACI-0204932" }, { "agency": "NSF", "grant_number": "CCF-0448835" }, { "agency": "Charles Lee Powell Foundation" }, { "agency": "Ralph M. Parsons Foundation" } ] }, "doi": "10.1137/060651100", "primary_object": { "basename": "DIRsiamrev07.pdf", "url": "https://authors.library.caltech.edu/records/p98fy-fvv11/files/DIRsiamrev07.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Dirks, Robert M.; Bois, Justin S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xv2ha-mzt94", "eprint_id": 22752, "eprint_status": "archive", "datestamp": "2023-08-22 07:50:26", "lastmod": "2023-10-23 17:10:34", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "White-Kristin-S", "name": { "family": "White", "given": "Kristin S." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Construction of an in vitro bistable circuit from synthetic transcriptional switches", "ispublished": "pub", "full_text_status": "public", "keywords": "bistability; ultrasensitivity; design principles; dynamical systems; transcription", "note": "\u00a9 2006 EMBO and Nature Publishing Group. Open Access. \n\nReceived 12 July 2006; Accepted 30 August 2006; Published online 12 December 2006.\nWe thank Y Zuo, ZF Cheng, A Malhotra, and MP Deutscher for their\nkind gift of RNases; KL Ho, C Wierzynski, D Stick, RM Murray, and\nCDS 273 students for helpful discussion on modeling; DY Zhang,\nS Mohanty, PWK Rothemund, G Seelig, JJ Hopfield, S Leibler, and\nB Yurke for discussion. Supported by ONR YIP Award No.\nN000140110813 and NSF ITR Award No. 0113443 to E Winfree and\nNSF NIRT Award No. 0103002 to N Seeman.\n\nPublished - bistable_switch2006_1_.pdf
Supplemental Material - bistable_switch2006_supp_1_.pdf
", "abstract": "Information processing using biochemical circuits is essential for survival and reproduction of\nnatural organisms. As stripped-down analogs of genetic regulatory networks in cells, we engineered\nartificial transcriptional networks consisting of synthetic DNA switches, regulated by RNA signals\nacting as transcription repressors, and two enzymes, bacteriophage T7 RNA polymerase and\nEscherichia coli ribonuclease H. The synthetic switch design is modular with programmable\nconnectivity and allows dynamic control of RNA signals through enzyme-mediated production\nand degradation. The switches support sharp and adjustable thresholds using a competitive\nhybridization mechanism, allowing arbitrary analog or digital circuits to be created in principle.\nAs an example, we constructed an in vitro bistable memory by wiring together two synthetic\nswitches and performed a systematic quantitative characterization. Good agreement between\nexperimental data and a simple mathematical model was obtained for switch input/output\nfunctions, phase plane trajectories, and the bifurcation diagram for bistability. Construction of\nlarger synthetic circuits provides a unique opportunity for evaluating model inference, prediction,\nand design of complex biochemical systems and could be used to control nanoscale devices and\nartificial cells.", "date": "2006-12-12", "date_type": "published", "publication": "Molecular Systems Biology", "volume": "2", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 68", "id_number": "CaltechAUTHORS:20110309-104200419", "issn": "1744-4292", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104200419", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Office of Naval Research (ONR)", "grant_number": "N000140110813" }, { "agency": "NSF", "grant_number": "CCF-0113443" }, { "agency": "NSF", "grant_number": "CBET-0103002" } ] }, "doi": "10.1038/msb4100099", "pmcid": "PMC1762086", "primary_object": { "basename": "bistable_switch2006_supp_1_.pdf", "url": "https://authors.library.caltech.edu/records/xv2ha-mzt94/files/bistable_switch2006_supp_1_.pdf" }, "related_objects": [ { "basename": "bistable_switch2006_1_.pdf", "url": "https://authors.library.caltech.edu/records/xv2ha-mzt94/files/bistable_switch2006_1_.pdf" } ], "resource_type": "article", "pub_year": "2006", "author_list": "Kim, Jongmin; White, Kristin S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/vf8a9-45s13", "eprint_id": 22753, "eprint_status": "archive", "datestamp": "2023-08-19 19:03:37", "lastmod": "2023-10-23 17:10:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Zhang-David-Yu", "name": { "family": "Zhang", "given": "David Yu" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Enzyme-free nucleic acid logic circuits", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2006 American Association for the Advancement of Science. \n\nReceived for publication 14 July 2006. Accepted for publication 13 November 2006. \n\nWe thank N. Dabby for a very close reading of this paper and extensive revisions. B. Yurke built the custom fluorometer used for these experiments, and we are further indebted to him for inspiration and advice. G.S. was supported by the Swiss National Science Foundation, the Center for Biological Circuit Design at the California Institute of Technology, and the NSF grant CHE-0533065 (Chemical Bonding Center) to M. N. Stojanovic. E.W. acknowledges NSF awards no. 0093846 and no. 0506468, and Human Frontier Science Program award no. RGY0074/2006-C.D.S. and D.Y.Z. were partially supported by a National Institute of Mental Health Training Grant to the Computation and Neural Systems option at the California Institute of Technology. D.Y.Z. was partially supported by a California Institute of Technology Grubstake award.\n\nSupplemental Material - DNA_logic_circuits2006_supp.pdf
", "abstract": "Biological organisms perform complex information processing and control tasks using sophisticated biochemical circuits, yet the engineering of such circuits remains ineffective compared with that of electronic circuits. To systematically create complex yet reliable circuits, electrical engineers use digital logic, wherein gates and subcircuits are composed modularly and signal restoration prevents signal degradation. We report the design and experimental implementation of DNA-based digital logic circuits. We demonstrate AND, OR, and NOT gates, signal restoration, amplification, feedback, and cascading. Gate design and circuit construction is modular. The gates use single-stranded nucleic acids as inputs and outputs, and the mechanism relies exclusively on sequence recognition and strand displacement. Biological nucleic acids such as microRNAs can serve as inputs, suggesting applications in biotechnology and bioengineering.", "date": "2006-12-08", "date_type": "published", "publication": "Science", "volume": "314", "number": "5805", "publisher": "American Association for the Advancement of Science", "pagerange": "1585-1588", "id_number": "CaltechAUTHORS:20110309-104200565", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104200565", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "Caltech Center for Biological Circuit Design" }, { "agency": "NSF", "grant_number": "CHE-0533065" }, { "agency": "NSF", "grant_number": "0093846" }, { "agency": "NSF", "grant_number": "DMS-0506468" }, { "agency": "Human Frontier Science Program", "grant_number": "RGY0074/2006" }, { "agency": "NIH Predoctoral Fellowship" }, { "agency": "Caltech Grubstake award" } ] }, "doi": "10.1126/science.1132493", "primary_object": { "basename": "DNA_logic_circuits2006_supp.pdf", "url": "https://authors.library.caltech.edu/records/vf8a9-45s13/files/DNA_logic_circuits2006_supp.pdf" }, "resource_type": "article", "pub_year": "2006", "author_list": "Seelig, Georg; Soloveichik, David; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/549jn-ecp58", "eprint_id": 22755, "eprint_status": "archive", "datestamp": "2023-08-19 18:37:42", "lastmod": "2023-10-23 17:10:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Catalyzed relaxation of a metastable DNA fuel", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2006 American Chemical Society.\n\nReceived May 22, 2006. Publication Date (Web): August 26, 2006. \n\nWe thank Richard W. Roberts for use of his Elutrap. G.S. was supported by the Swiss National Science Foundation and the Center for Biological Circuit design at Caltech. E.W. acknowledges NSF Awards #0093846, #0533064, and #0506468. B.Y. thanks the Moore Foundation for a Moore Distinguished Scholar Fellowship. Preliminary results for this\nwork were previously reported.[37]", "abstract": "Practically all of life's molecular processes, from chemical synthesis to replication, involve enzymes that carry out their functions through\n the catalytic transformation of metastable fuels into waste products.\n Catalytic control of reaction rates will prove to be as useful and\n ubiquitous in nucleic-acid-based engineering as it is in biology. Here\n we report a metastable DNA \"fuel\" and a corresponding DNA\n \"catalyst\" that improve upon the original hybridization-based\n catalyst system (Turberfield et al. Phys. Rev. Lett. 90,\n 118102-1118102-4) by more than 2 orders of magnitude. This is achieved\n by identifying and purifying a fuel with a kinetically trapped\n metastable configuration consisting of a \"kissing loop\" stabilized\n by flanking helical domains; the catalyst strand acts by opening a\n helical domain and allowing the complex to relax to its ground state by\n a multistep pathway. The improved fuel/catalyst system shows a roughly\n 5000-fold acceleration of the uncatalyzed reaction, with each catalyst\n molecule capable of turning over in excess of 40 substrates. With\n k_(cat)/K_M \u2248 10^7/M/min, comparable to many protein\n enzymes and ribozymes, this fuel system becomes a viable component\n enabling future DNA-based synthetic molecular machines and logic\n circuits. As an example, we designed and characterized a signal\n amplifier based on the fuel-catalyst system. The amplifier uses a\n single strand of DNA as input and releases a second strand with\n unrelated sequence as output. A single input strand can catalytically\n trigger the release of more than 10 output strands.", "date": "2006-09-20", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "128", "number": "37", "publisher": "American Chemical Society", "pagerange": "12211-12220", "id_number": "CaltechAUTHORS:20110309-104200898", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104200898", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "Caltech Center for Biological Circuit Design" }, { "agency": "NSF", "grant_number": "0093846" }, { "agency": "NSF", "grant_number": "CHE-0533064" }, { "agency": "NSF", "grant_number": "DMS-0506468" }, { "agency": "Gordon and Betty Moore Foundation" } ] }, "doi": "10.1021/ja0635635", "resource_type": "article", "pub_year": "2006", "author_list": "Seelig, Georg; Yurke, Bernard; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/awcyr-76y79", "eprint_id": 24776, "eprint_status": "archive", "datestamp": "2023-08-19 17:01:57", "lastmod": "2023-10-24 14:55:21", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Algorithmic Self-Assembly of DNA", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2006 IEEE.\n\nIssue Date: 9-12 May 2006; Date of Current Version: 30 July 2007.", "abstract": "Nucleic acids have proven to be remarkably versatile as an engineering material for chemical tasks including the storage of information, catalyzing reactions creating and breaking bonds, mechanical manipulation using molecular motors, and constructing supramolecular structures. This talk will focus particularly on molecular self-assembly, giving examples of engineered DNA \"tiles\" that crystallize into two-dimensional sheets, one-dimensional tubes and ribbons, and information-guided patterns such as a Sierpinski triangle and a binary counter. A theme is how cooperative binding can be used to control nucleation and direct selective tile attachment. Such \"algorithmic\" self-assembly may provide a bottom-up fabrication method for creating complex, well-defined supramolecular structures that can be used as scaffolds or templates for applications such as arranging molecular electronic components into active circuits.", "date": "2006", "date_type": "published", "publisher": "IEEE", "place_of_pub": "Piscataway, NJ", "pagerange": "4-4", "id_number": "CaltechAUTHORS:20110810-095116353", "isbn": "978-1-4244-0337-0", "book_title": "Proceedings of the 2006 International Conference on Microtechnologies in Medicine and Biology", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110810-095116353", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "other_numbering_system": { "items": [ { "id": "9296580", "name": "INSPEC Accession Number" } ] }, "resource_type": "book_section", "pub_year": "2006", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f3tmg-p8p50", "eprint_id": 22756, "eprint_status": "archive", "datestamp": "2023-08-19 16:55:57", "lastmod": "2024-01-13 00:10:53", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Complexity of compact proofreading for self-assembled patterns", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2006 Springer-Verlag Berlin Heidelberg. \n\nWe thank Ho-Lin Chen, Ashish Goel, Paul Rothemund, Matthew Cook, and Nata\u0161a Jonoska for discussions that greatly contributed to this work. This work was supported by NSF NANO Grant No. 0432193.\n\nSubmitted - fragile_patterns_preprint_1_.pdf
", "abstract": "Fault-tolerance is a critical issue for biochemical computation. Recent theoretical work on algorithmic self-assembly has shown that error\n correcting tile sets are possible, and that they can achieve\n exponential decrease in error rates with a small increase in the number\n of tile types and the scale of the construction [24, 4]. Following\n [17], we consider the issue of applying similar schemes to achieve\n error correction without any increase in the scale of the assembled\n pattern. Using a new proofreading transformation, we show that compact\n proofreading can be performed for some patterns with a modest increase\n in the number of tile types. Other patterns appear to require an\n exponential number of tile types. A simple property of existing\n proofreading schemes - a strong kind of redundancy - is the culprit,\n suggesting that if general purpose compact proofreading schemes are to\n be found, this type of redundancy must be avoided.", "date": "2006", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "305-324", "id_number": "CaltechAUTHORS:20110309-104201054", "isbn": "3-540-34161-7", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104201054", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0432193" } ] }, "contributors": { "items": [ { "id": "Carbone-A", "name": { "family": "Carbone", "given": "Alessandra" } }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." } } ] }, "doi": "10.1007/11753681_24", "primary_object": { "basename": "fragile_patterns_preprint_1_.pdf", "url": "https://authors.library.caltech.edu/records/f3tmg-p8p50/files/fragile_patterns_preprint_1_.pdf" }, "resource_type": "book_section", "pub_year": "2006", "author_list": "Soloveichik, David and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/e41xe-mmr22", "eprint_id": 98100, "eprint_status": "archive", "datestamp": "2023-08-19 17:08:15", "lastmod": "2024-01-14 21:52:55", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Fault-Tolerance in Biochemical Systems", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2006 Springer-Verlag Berlin Heidelberg.", "abstract": "Biochemistry is messy. It's a miracle any of it works. And yet it does. The wonderful diversity and amazing talents of living things derive from the biochemical processes that copy genetic information and use that information as a program to construct a sophisticated organization of matter and behaviour \u2013 reliably and robustly overcoming insult after insult from the environment. In this talk I will first discuss how known techniques for fault-tolerant computing, such as von Neumann's multiplexing technique for digital circuits, can be translated to the biochemical context. I will then discuss fault-tolerance in molecular self-assembly, which requires new techniques. Using a model of algorithmic self-assembly, a generalization of crystal growth processes, I will present techniques for controlling the nucleation of self-assembly, for reducing errors during growth, and for recovering after gross damage or fragmentation.", "date": "2006", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "26", "id_number": "CaltechAUTHORS:20190822-092012516", "isbn": "978-3-540-38593-6", "book_title": "Unconventional Computation", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190822-092012516", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Calude-C-S", "name": { "family": "Calude", "given": "Cristian S." } }, { "id": "Dinneen-M-J", "name": { "family": "Dinneen", "given": "Michael J." } }, { "id": "P\u0103un-G", "name": { "family": "P\u0103un", "given": "Gheorghe" } }, { "id": "Rozenberg-G", "name": { "family": "Rozenberg", "given": "Grzegorz" } }, { "id": "Stepney-S", "name": { "family": "Stepney", "given": "Susan" } } ] }, "doi": "10.1007/11839132_3", "resource_type": "book_section", "pub_year": "2006", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cdegn-xhs37", "eprint_id": 27350, "eprint_status": "archive", "datestamp": "2023-08-19 17:04:09", "lastmod": "2024-01-13 05:43:58", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Self-Healing Tile Sets", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2006 Springer. \n\nThe author is indebted to discussions with Ashish Goel, Ho-Lin Chen, Rebecca Schulman, David Soloveichik, Matthew Cook, and Paul Rothemund. This work was partially funded by NSF award #0523761.\n\nSubmitted - self_healing_paper_1_.pdf
", "abstract": "Biology provides the synthetic chemist with a tantalizing and frustrating challenge:\nto create complex objects, defined from the molecular scale up to meters,\nthat construct themselves from elementary components, and perhaps\neven reproduce themselves. This is the challenge of bottom-up fabrication.\nThe most compelling answer to this challenge was formulated in the early\n1980s by Ned Seeman, who realized that the information carried by DNA\nstrands provides a means to program molecular self-assembly, with potential\napplications including DNA scaffolds for crystallography [19] or for molecular\nelectronic circuits [15]. This insight opened the doors to engineering with the\nrich set of phenomena available in nucleic acid chemistry [20].", "date": "2006", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "55-78", "id_number": "CaltechAUTHORS:20111021-093324589", "isbn": "9783540302964", "book_title": "Nanotechnology: Science and Computation", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111021-093324589", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0523761" } ] }, "contributors": { "items": [ { "id": "Chen-Junghuei", "name": { "family": "Chen", "given": "Junghuei" } }, { "id": "Jonoska-N", "name": { "family": "Jonoska", "given": "Nata\u0161a" } }, { "id": "Rozenberg-G", "name": { "family": "Rozenberg", "given": "Grzegorz" } } ] }, "doi": "10.1007/3-540-30296-4_4", "primary_object": { "basename": "self_healing_paper_1_.pdf", "url": "https://authors.library.caltech.edu/records/cdegn-xhs37/files/self_healing_paper_1_.pdf" }, "resource_type": "book_section", "pub_year": "2006", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5e5ep-78851", "eprint_id": 22757, "eprint_status": "archive", "datestamp": "2023-08-19 16:42:56", "lastmod": "2023-10-23 17:10:54", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Barish-R-D", "name": { "family": "Barish", "given": "Robert D." } }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Two computational primitives for algorithmic self-assembly: Copying and counting", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2005 American Chemical Society. \n\nReceived October 14, 2005; Revised Manuscript Received October 29, 2005. Publication Date (Web): November 23, 2005. \n\nFor useful discussions we thank Rebecca Schulman and Deborah Fygenson. We thank the Caltech Molecular Materials Research Center for use of their AFM scanners. R.D.B. was partially supported by a Thomas E. Everhart Caltech Summer Undergraduate Research Fellowship (SURF). P.W.K.R. was supported by a Beckman Fellowship and Moore Center for the Physics of Information postdoctoral fellowship. E.W. acknowledges National Science Foundation awards 0093486 and 0432193.\n\nSupplemental Material - binary_counter_supp_NanoLetters_1_.pdf
", "abstract": "Copying and counting are useful primitive operations for computation and construction. We have made DNA crystals that copy and crystals that count as they grow. For counting, 16 oligonucleotides assemble into four DNA Wang tiles that subsequently crystallize on a polymeric nucleating scaffold strand, arranging themselves in a binary counting pattern that could serve as a template for a molecular electronic demultiplexing circuit. Although the yield of counting crystals is low, and per-tile error rates in such crystals is roughly 10%, this work demonstrates the potential of algorithmic self-assembly to create complex nanoscale patterns of technological interest. A subset of the tiles for counting form information-bearing DNA tubes that copy bit strings from layer to layer along their length.", "date": "2005-12", "date_type": "published", "publication": "Nano Letters", "volume": "5", "number": "12", "publisher": "American Chemical Society", "pagerange": "2586-2592", "id_number": "CaltechAUTHORS:20110309-104201220", "issn": "1530-6984", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104201220", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "Moore Center for the Physics of Information Postdoctoral Fellowship" }, { "agency": "NSF", "grant_number": "0093486" }, { "agency": "NSF", "grant_number": "0432193" } ] }, "doi": "10.1021/nl052038l", "primary_object": { "basename": "binary_counter_supp_NanoLetters_1_.pdf", "url": "https://authors.library.caltech.edu/records/5e5ep-78851/files/binary_counter_supp_NanoLetters_1_.pdf" }, "resource_type": "article", "pub_year": "2005", "author_list": "Barish, Robert D.; Rothemund, Paul W. K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jv7sr-1cc79", "eprint_id": 22759, "eprint_status": "archive", "datestamp": "2023-08-22 04:27:24", "lastmod": "2023-10-23 17:11:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-D", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "The computational power of Benenson automata", "ispublished": "pub", "full_text_status": "public", "keywords": "molecular computing; DNA computing; computational complexity; restriction enzymes; branching programs; circuit complexity", "note": "\u00a9 2005 Elsevier B.V. \n\nReceived 21 December 2004; revised 29 July 2005; Accepted 29 July 2005. Communicated by T. Yokomori. Available online 24 August 2005. \n\nWe thank Georg Seelig for first bringing Benenson et al.'s work to our attention. Further, we thank two anonymous reviewers for very detailed reading of this paper and useful suggestions. This research was supported by NIH training Grant MH19138-15.\n\nSubmitted - benenson_preprint.pdf
", "abstract": "The development of autonomous molecular computers capable of making independent decisions in vivo regarding local drug administration may revolutionize medical science. Recently Benenson et al. [An autonomous molecular computer for logical control of gene expression, Nature 429 (2004) 423\u2013429.] have envisioned one form such a \"smart drug\" may take by implementing an in vitro scheme, in which a long DNA state molecule is cut repeatedly by a restriction enzyme in a manner dependent upon the presence of particular short DNA \"rule molecules.\" To analyze the potential of their scheme in terms of the kinds of computations it can perform, we study an abstraction assuming that a certain class of restriction enzymes is available and reactions occur without error. We also discuss how our molecular algorithms could perform with known restriction enzymes. By exhibiting a way to simulate arbitrary circuits, we show that these \"Benenson automata\" are capable of computing arbitrary Boolean functions. Further, we show that they are able to compute efficiently exactly those functions computable by log-depth circuits. Computationally, we formalize a new variant of limited width branching programs with a molecular implementation.", "date": "2005-11-17", "date_type": "published", "publication": "Theoretical Computer Science", "volume": "344", "number": "2-3", "publisher": "Elsevier", "pagerange": "279-297", "id_number": "CaltechAUTHORS:20110309-104201537", "issn": "0304-3975", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104201537", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "MH19138-15" } ] }, "doi": "10.1016/j.tcs.2005.07.027", "primary_object": { "basename": "benenson_preprint.pdf", "url": "https://authors.library.caltech.edu/records/jv7sr-1cc79/files/benenson_preprint.pdf" }, "resource_type": "article", "pub_year": "2005", "author_list": "Soloveichik, David and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4v9eb-j1b49", "eprint_id": 101452, "eprint_status": "archive", "datestamp": "2023-08-19 15:10:54", "lastmod": "2024-01-14 22:07:38", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Soloveichik-David", "name": { "family": "Soloveichik", "given": "David" }, "orcid": "0000-0002-2585-4120" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Complexity of Self-assembled Shapes (Extended Abstract)", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2005 Springer-Verlag Berlin Heidelberg. \n\nWe thank Len Adleman, members of his group, and Paul Rothemund for fruitful discussions and suggestions. We thank Rebecca Schulman and David Zhang for useful and entertaining conversations about descriptional complexity of tile systems. This work was supported by NSF CAREER Grant No. 0093486.\n\nSubmitted - 0412096.pdf
", "abstract": "The connection between self-assembly and computation suggests that a shape can be considered the output of a self-assembly \"program,\" a set of tiles that fit together to create a shape. It seems plausible that the size of the smallest self-assembly program that builds a shape and the shape's descriptional (Kolmogorov) complexity should be related. We show that under the notion of a shape that is independent of scale this is indeed so: in the Tile Assembly Model, the minimal number of distinct tile types necessary to self-assemble an arbitrarily scaled shape can be bounded both above and below in terms of the shape's Kolmogorov complexity. As part of the proof of the main result, we sketch a general method for converting a program outputting a shape as a list of locations into a set of tile types that self-assembles into a scaled up version of that shape. Our result implies, somewhat counter-intuitively, that self-assembly of a scaled up version of a shape often requires fewer tile types, and suggests that the independence of scale in self-assembly theory plays the same crucial role as the independence of running time in the theory of computability.", "date": "2005", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "344-354", "id_number": "CaltechAUTHORS:20200221-095747956", "isbn": "978-3-540-26174-2", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200221-095747956", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" } ] }, "contributors": { "items": [ { "id": "Ferretti-Claudio", "name": { "family": "Ferretti", "given": "Claudio" } }, { "id": "Mauri-Giancarlo", "name": { "family": "Mauri", "given": "Giancarlo" } }, { "id": "Zandron-Claudio", "name": { "family": "Zandron", "given": "Claudio" } } ] }, "doi": "10.1007/11493785_30", "primary_object": { "basename": "0412096.pdf", "url": "https://authors.library.caltech.edu/records/4v9eb-j1b49/files/0412096.pdf" }, "resource_type": "book_section", "pub_year": "2005", "author_list": "Soloveichik, David and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yyhd4-hwj78", "eprint_id": 22761, "eprint_status": "archive", "datestamp": "2023-08-19 14:56:41", "lastmod": "2024-01-13 00:10:57", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Seelig-G", "name": { "family": "Seelig", "given": "Georg" } }, { "id": "Yurke-B", "name": { "family": "Yurke", "given": "Bernard" }, "orcid": "0000-0003-3913-2855" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "DNA hybridization catalysts and catalyst circuits", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2005 Springer-Verlag Berlin Heidelberg. \n\nThanks to Ben Rahn, Jeremy Leibs, Joseph Schaeffer, Jongmin Kim, Dave Zhang, and especially Paul Rothemund for stimulating discussion and help preparing figures and simulations. GS was supported by the\nSwiss National Science Foundation, EW was supported by NSF CAREER Grant No. 0093486, NSF ITR Grant No. 0113443, and GenTel.\n\nSubmitted - catalysts_DNA10_preprint.pdf
", "abstract": "Practically all of life's molecular processes, from chemical synthesis to replication, involve enzymes that carry out their functions through the catalysis of metastable fuels into waste products. Catalytic control of reaction rates will prove to be as useful and ubiquitous in\nDNA nanotechnology as it is in biology. Here we present experimental results on the control of the decay rates of a metastable DNA \"fuel\". We show that the fuel complex can be induced to decay with a rate about 1600 times faster than it would decay spontaneously. The original DNA hybridization catalyst [15] achieved a maximal speed-up of roughly 30. The fuel complex discussed here can therefore serve as the basic ingredient for an improved DNA hybridization catalyst. As an example application for DNA hybridization catalysts, we propose a method for implementing arbitrary digital logic circuits.", "date": "2005", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "329-343", "id_number": "CaltechAUTHORS:20110309-104201845", "isbn": "3-540-26174-5", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104201845", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "NSF", "grant_number": "CCF-0113443" }, { "agency": "GenTel" } ] }, "contributors": { "items": [ { "id": "Ferretti-C", "name": { "family": "Ferretti", "given": "Claudio" } }, { "id": "Mauri-G", "name": { "family": "Mauri", "given": "Giancarlo" } }, { "id": "Zandron-C", "name": { "family": "Zandron", "given": "Claudio" } } ] }, "doi": "10.1007/11493785_29", "primary_object": { "basename": "catalysts_DNA10_preprint.pdf", "url": "https://authors.library.caltech.edu/records/yyhd4-hwj78/files/catalysts_DNA10_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2005", "author_list": "Seelig, Georg; Yurke, Bernard; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f428a-gx176", "eprint_id": 101473, "eprint_status": "archive", "datestamp": "2023-08-22 02:57:02", "lastmod": "2024-01-14 22:07:49", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-Rebecca", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Programmable Control of Nucleation for Algorithmic Self-assembly", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Critical Nucleus; Mismatch Error; Target Strand; Facet Error; Tile Assembly Model", "note": "\u00a9 2005 Springer-Verlag Berlin Heidelberg. \n\nThe authors are grateful to Ho-Lin Chen, Ashish Goel, Rizal Hariadi, Paul Rothemund, Bernie Yurke, and Dave Zhang for helpful advice and discussions. This work was supported by NSF CAREER Grant No. 0093486 to EW and an NSF Graduate Fellowship to RS.", "abstract": "Algorithmic self-assembly has been proposed as a mechanism for autonomous DNA computation and for bottom-up fabrication of complex nanodevices. Whereas much previous work has investigated self-assembly programs using an abstract model of irreversible, errorless assembly, experimental studies as well as more sophisticated reversible kinetic models indicate that algorithmic self-assembly is subject to several kinds of errors. Previously, it was shown that proofreading tile sets can reduce the occurrence of mismatch and facet errors. Here, we introduce the zig-zag tile set, which can reduce the occurrence of spurious nucleation errors. The zig-zag tile set takes advantage of the fact that assemblies must reach a critical size before their growth becomes favorable. By using a zig-zag tile set of greater width, we can increase the critical size of spurious assemblies without increasing the critical size of correctly seeded assemblies, exponentially reducing the spurious nucleation rate. In combination with proofreading results, this result indicates that algorithmic self-assembly can be performed with low error rates without a significant reduction in assembly speed. Furthermore, our zig-zag boundaries suggest methods for exquisite detection of DNA strands and for the replication of inheritable information without the use of enzymes.", "date": "2005", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "319-328", "id_number": "CaltechAUTHORS:20200221-152848969", "isbn": "978-3-540-26174-2", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200221-152848969", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "contributors": { "items": [ { "id": "Ferretti-Claudio", "name": { "family": "Ferretti", "given": "Claudio" } }, { "id": "Mauri-Giancarlo", "name": { "family": "Mauri", "given": "Giancarlo" } }, { "id": "Zandron-Claudio", "name": { "family": "Zandron", "given": "Claudio" } } ] }, "doi": "10.1007/11493785_28", "resource_type": "book_section", "pub_year": "2005", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/j4yzg-a7236", "eprint_id": 22758, "eprint_status": "archive", "datestamp": "2023-08-19 14:56:34", "lastmod": "2024-01-13 00:10:55", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Self-replication and evolution of DNA crystals", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2005 Springer-Verlag Berlin Heidelberg.\n\nWe would like to thank Bernie Yurke, Gerald Joyce,\nAndy Ellington, Graham Cairns-Smith, Paul Rothemund, Dave Zhang and David\nSoloveichik for helpful discussion on sequence amplification and evolution. The\nAFM image in the inset of Figure 1c was taken by Ho-Lin Chen. This research\nwas partially supported by NSF awards #0093486 and #0432193.\n\nSubmitted - dna-crystal-evolution_preprint.pdf
", "abstract": "Is it possible to create a simple physical system that is capable of replicating itself? Can such a system evolve interesting behaviors, thus allowing it to adapt to a wide range of environments? This paper presents a design for such a replicator constructed exclusively from synthetic DNA. The basis for the replicator is crystal growth: information is stored in the spatial arrangement of monomers and copied from layer to layer by templating. Replication is achieved by fragmentation of crystals, which produces new crystals that carry the same information. Crystal replication avoids intrinsic problems associated with template-directed mechanisms for replication of one-dimensional polymers. A key innovation of our work is that by using programmable DNA tiles as the crystal monomers, we can design crystal growth processes that apply interesting selective pressures to the evolving sequences. While evolution requires that copying occur with high accuracy, we show how to adapt error-correction techniques from algorithmic self-assembly to lower the replication error rate as much as is required.", "date": "2005", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "734-743", "id_number": "CaltechAUTHORS:20110309-104201367", "isbn": "3-540-28848-1", "book_title": "Advances in Artificial Life", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104201367", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCF-0093486" }, { "agency": "NSF", "grant_number": "CCF-0432193" } ] }, "contributors": { "items": [ { "id": "Bentley-P-J", "name": { "family": "Bentley", "given": "Peter J." } }, { "id": "Capcarrere-M-S", "name": { "family": "Capcarrere", "given": "Mathieu S." } }, { "id": "Freitas-A-A", "name": { "family": "Freitas", "given": "Alex A." } }, { "id": "Johnson-C-G", "name": { "family": "Johnson", "given": "Colin G." } }, { "id": "Timmis-J", "name": { "family": "Timmis", "given": "Jon" } } ] }, "doi": "10.1007/11553090_74", "primary_object": { "basename": "dna-crystal-evolution_preprint.pdf", "url": "https://authors.library.caltech.edu/records/j4yzg-a7236/files/dna-crystal-evolution_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2005", "author_list": "Schulman, Rebecca and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5884w-g9h71", "eprint_id": 22765, "eprint_status": "archive", "datestamp": "2023-08-19 14:54:40", "lastmod": "2023-10-23 17:11:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Ekani-Nkodo-A", "name": { "family": "Ekani-Nkodo", "given": "Axel" } }, { "id": "Papadakis-N", "name": { "family": "Papadakis", "given": "Nick" } }, { "id": "Kumar-A", "name": { "family": "Kumar", "given": "Ashish" } }, { "id": "Fygenson-D-K", "name": { "family": "Fygenson", "given": "Deborah Kuchnir" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Design and characterization of programmable DNA nanotubes", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2004 American Chemical Society. \n\nReceived September 17, 2004. Publication Date (Web): November 24, 2004. \n\nFor useful discussions we thank Matthew Cook and Hideo Mabuchi. We thank the Caltech Molecular Materials Research Center for use of their AFM scanners. P.W.K.R. was supported by a Beckman Fellowship. This work was supported in part by National Science Foundation CAREER Grant No. 0093486 and MRSEC Award DMR00-80034, DARPA BioComputation Contract F30602-01-2-0561, NASA NRA2-37143, an Army Research Office/UCSB Institute for Collaborative Biotechnologies Grant, an Alfred P. Sloan Foundation Fellowship (D.K.F.), and a grant from GenTel Corporation.\n\nSupplemental Material - ja044319lsi20040917_035440.mpg
Supplemental Material - ja044319lsi20040917_035521.mpg
Supplemental Material - ja044319lsi20040917_035648.mpg
Supplemental Material - ja044319lsi20041022_031528.pdf
", "abstract": "DNA self-assembly provides a programmable bottom-up approach for the synthesis of complex structures from nanoscale components. Although nanotubes are a fundamental form encountered in tile-based DNA self-assembly, the factors governing tube structure remain poorly understood. Here we report and characterize a new type of nanotube made from DNA double-crossover molecules (DAE-E tiles). Unmodified tubes range from 7 to 20 nm in diameter (4 to 10 tiles in circumference), grow as long as 50 \u03bcm with a persistence length of ~4 \u03bcm, and can be programmed to display a variety of patterns. A survey of modifications (1) confirms the importance of sticky-end stacking, (2) confirms the identity of the inside and outside faces of the tubes, and (3) identifies features of the tiles that profoundly affect the size and morphology of the tubes. Supported by these results, nanotube structure is explained by a simple model based on the geometry and energetics of B-form DNA.", "date": "2004-12-22", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "126", "number": "50", "publisher": "American Chemical Society", "pagerange": "16344-16352", "id_number": "CaltechAUTHORS:20110309-104202496", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104202496", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "NSF", "grant_number": "0093486" }, { "agency": "NSF", "grant_number": "DMR00-80034" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "F30602-01-2-0561" }, { "agency": "NASA", "grant_number": "NRA2-37143" }, { "agency": "Army Research Office (ARO)" }, { "agency": "Alfred P. Sloan Foundation" }, { "agency": "GenTel Corporation" } ] }, "doi": "10.1021/ja044319l", "primary_object": { "basename": "ja044319lsi20040917_035440.mpg", "url": "https://authors.library.caltech.edu/records/5884w-g9h71/files/ja044319lsi20040917_035440.mpg" }, "related_objects": [ { "basename": "ja044319lsi20040917_035521.mpg", "url": "https://authors.library.caltech.edu/records/5884w-g9h71/files/ja044319lsi20040917_035521.mpg" }, { "basename": "ja044319lsi20040917_035648.mpg", "url": "https://authors.library.caltech.edu/records/5884w-g9h71/files/ja044319lsi20040917_035648.mpg" }, { "basename": "ja044319lsi20041022_031528.pdf", "url": "https://authors.library.caltech.edu/records/5884w-g9h71/files/ja044319lsi20041022_031528.pdf" } ], "resource_type": "article", "pub_year": "2004", "author_list": "Rothemund, Paul W. K.; Ekani-Nkodo, Axel; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ceqqb-q4p03", "eprint_id": 290, "eprint_status": "archive", "datestamp": "2023-08-22 02:44:41", "lastmod": "2023-10-13 20:36:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Papadakis-N", "name": { "family": "Papadakis", "given": "Nick" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Algorithmic Self-Assembly of DNA Sierpinski Triangles", "ispublished": "pub", "full_text_status": "public", "keywords": "AFM, atomic force microscopy; aTAM, abstract Tile Assembly Model; 1D, one-dimensional; 2D, two-dimensional; DNA, deoxyribonucleic acid; DAE-E, double-crossover, antiparallel, even intramolecular spacing, even intermolecular spacing; DAO-E, double-crossover, antiparallel, odd intramolecular spacing, even intermolecular spacing; kTAM, kinetic Tile Assembly Model; PCR, polymerase chain reaction; RAM, random-access memory; XOR, exclusive or", "note": "\u00a9 2004 Rothemund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived September 14, 2004; Accepted October 5, 2004; Published December 7, 2004. \n\nFor discussions, insights, and advice, we thank John Hopfield, Ned Seeman, Len Adleman, Matt Cook, Hui Wang, Rebecca Schulman, Shaun Lee, Rizal Hariadi, and Jason Rolfe. Experiments described in Figure S18 were performed by Jason Rolfe. We thank the Caltech Molecular Materials Research Center for use of their AFM scanners. PWKR was supported by a Beckman Fellowship. This work was supported in part by the National Science Foundation PECASE EIA-0093486, DARPA BioComputation F30602-01-2-0561, NASA NRA2-37143, and GenTel Corporation. \n\nConflicts of interest: The authors have declared that no conflicts of interest exist. \n\nAuthor contributions: PWKR and EW conceived and designed the experiments. PWKR, NP, and EW performed the experiments. PWKR and EW analyzed the data. PWKR and EW wrote the paper.\n\nPublished - ROTpb04.pdf
", "abstract": "Algorithms and information, fundamental to technological and biological organization, are also an essential aspect of many elementary physical phenomena, such as molecular self-assembly. Here we report the molecular realization, using two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update rule computes the binary function XOR and thus fabricates a fractal pattern \u2014 a Sierpinski triangle \u2014 as it grows. To achieve this, abstract tiles were translated into DNA tiles based on double-crossover motifs. Serving as input for the computation, long single-stranded DNA molecules were used to nucleate growth of tiles into algorithmic crystals. For both of two independent molecular realizations, atomic force microscopy revealed recognizable Sierpinski triangles containing 100\u2013200 correct tiles. Error rates during assembly appear to range from 1% to 10%. Although imperfect, the growth of Sierpinski triangles demonstrates all the necessary mechanisms for the molecular implementation of arbitrary cellular automata. This shows that engineered DNA self-assembly can be treated as a Turing-universal biomolecular system, capable of implementing any desired algorithm for computation or construction tasks.", "date": "2004-12", "date_type": "published", "publication": "PLoS Biology", "volume": "2", "number": "12", "publisher": "Public Library of Science", "pagerange": "2041-2053", "id_number": "CaltechAUTHORS:ROTpb04", "issn": "1544-9173", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:ROTpb04", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "EIA-0093486" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "F30602-01-2-0561" }, { "agency": "NASA", "grant_number": "NRA2-37143" }, { "agency": "GenTel Corporation" } ] }, "doi": "10.1371/journal.pbio.0020424", "pmcid": "PMC534809", "primary_object": { "basename": "ROTpb04.pdf", "url": "https://authors.library.caltech.edu/records/ceqqb-q4p03/files/ROTpb04.pdf" }, "resource_type": "article", "pub_year": "2004", "author_list": "Rothemund, Paul W. K.; Papadakis, Nick; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r694w-8cp52", "eprint_id": 22769, "eprint_status": "archive", "datestamp": "2023-08-19 13:02:57", "lastmod": "2023-10-23 17:11:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dirks-R-M", "name": { "family": "Dirks", "given": "Robert M." } }, { "id": "Lin-Milo-M", "name": { "family": "Lin", "given": "Milo" }, "orcid": "0000-0001-8680-2685" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Paradigms for computational nucleic acid design", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2004 Oxford University Press. \n\nReceived December 14, 2003; Revised and Accepted January 28, 2004. \n\nThe authors wish to thank D. Baker, A. Condon, S. L. Mayo, N. C. Seeman and R. Schulman for comments on the manuscript, and I. Hofacker for providing the kinetic simulation package Kinfold. The following research support is gratefully acknowledged: NSF graduate research fellowship (R.M.D.), Caltech Axline SURF (M.L.), DARPA and Air Force Research Laboratory under agreement F30602-01020561 (R.M.D., E.W. and N.A.P.) and Ralph M. Parsons Foundation (N.A.P.).\n\nPublished - 1392.full.pdf
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", "abstract": "The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR\u2010based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum free\u2010energy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are refined further. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape.", "date": "2004-02", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "32", "number": "4", "publisher": "Oxford University Press", "pagerange": "1392-1403", "id_number": "CaltechAUTHORS:20110309-104203820", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104203820", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Caltech Axline SURF" }, { "agency": "Air Force Research Laboratory", "grant_number": "F30602-01020561" }, { "agency": "Ralph M. Parsons Foundation" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" } ] }, "doi": "10.1093/nar/gkh291", "pmcid": "PMC390280", "primary_object": { "basename": "1392.full.pdf", "url": "https://authors.library.caltech.edu/records/r694w-8cp52/files/1392.full.pdf" }, "related_objects": [ { "basename": "design_nar2004_supplemental.pdf", "url": "https://authors.library.caltech.edu/records/r694w-8cp52/files/design_nar2004_supplemental.pdf" }, { "basename": "supp_resubmit.pdf", "url": "https://authors.library.caltech.edu/records/r694w-8cp52/files/supp_resubmit.pdf" } ], "resource_type": "article", "pub_year": "2004", "author_list": "Dirks, Robert M.; Lin, Milo; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tnqpv-xq834", "eprint_id": 27363, "eprint_status": "archive", "datestamp": "2023-08-19 12:45:08", "lastmod": "2023-10-24 17:05:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Jongmin", "name": { "family": "Kim", "given": "Jongmin" }, "orcid": "0000-0002-2713-1006" }, { "id": "Hopfield-J-J", "name": { "family": "Hopfield", "given": "John J." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Neural network computation by in vitro transcriptional circuits", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2004 MIT Press. \n\nWe thank Michael Elowitz, Paul Rothemund, Casimir Wierzynski, Dan Stick and David Zhang for valuable discussions, and ONR and NSF for funding.\n\nSubmitted - invitro_neural_nets_NIPS2004_1_.pdf
", "abstract": "The structural similarity of neural networks and genetic regulatory networks\nto digital circuits, and hence to each other, was noted from the\nvery beginning of their study [1, 2]. In this work, we propose a simple\nbiochemical system whose architecture mimics that of genetic regulation\nand whose components allow for in vitro implementation of arbitrary\ncircuits. We use only two enzymes in addition to DNA and RNA\nmolecules: RNA polymerase (RNAP) and ribonuclease (RNase). We\ndevelop a rate equation for in vitro transcriptional networks, and derive\na correspondence with general neural network rate equations [3].\nAs proof-of-principle demonstrations, an associative memory task and a\nfeedforward network computation are shown by simulation. A difference\nbetween the neural network and biochemical models is also highlighted:\nglobal coupling of rate equations through enzyme saturation can lead\nto global feedback regulation, thus allowing a simple network without\nexplicit mutual inhibition to perform the winner-take-all computation.\nThus, the full complexity of the cell is not necessary for biochemical\ncomputation: a wide range of functional behaviors can be achieved with\na small set of biochemical components.", "date": "2004", "date_type": "published", "publication": "Advances in Neural Information Processing Systems", "volume": "17", "publisher": "MIT Press", "pagerange": "681-688", "id_number": "CaltechAUTHORS:20111024-075732549", "issn": "1049-5258", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-075732549", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Office of Naval Research (ONR)" }, { "agency": "NSF" } ] }, "primary_object": { "basename": "invitro_neural_nets_NIPS2004_1_.pdf", "url": "https://authors.library.caltech.edu/records/tnqpv-xq834/files/invitro_neural_nets_NIPS2004_1_.pdf" }, "resource_type": "article", "pub_year": "2004", "author_list": "Kim, Jongmin; Hopfield, John J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1x89h-zdn73", "eprint_id": 22767, "eprint_status": "archive", "datestamp": "2023-08-19 12:43:07", "lastmod": "2024-01-13 00:11:01", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schulman-R", "name": { "family": "Schulman", "given": "Rebecca" }, "orcid": "0000-0003-4555-3162" }, { "id": "Lee-Shaun", "name": { "family": "Lee", "given": "Shaun" } }, { "id": "Papadakis-N", "name": { "family": "Papadakis", "given": "Nick" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "One dimensional boundaries for DNA tile self-assembly", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2004 Springer-Verlag Berlin Heidelberg.\nWe would like to thank Bernie Yurke for pointing out the effects of slight differences\nin stoichiometry, and for his very descriptive term \"stoichiometry poisoning\".\nPaul Rnthemund, Rizal Hariadi, and other members of the DNA Lab\nprovided helpful hints and stimulating conversation. This work was supported by\nNSF CAREER Grant No. 0093486, DARPA BioComputation Contract F30602-01-2-0561, NASA NRA2-37143, and GenTel.\n\nSubmitted - OneDimBoundaries_DNA9_preprint.pdf
", "abstract": "In this paper we report the design and synthesis of DNA molecules (referred to as DNA tiles) with specific binding interactions that\n guide self-assembly to make one-dimensional assemblies shaped as lines,\n V's and X's. These DNA tile assemblies have been visualized by atomic\n force microscopy. The highly-variable distribution of shapes - e.g.,\n the length of the arms of X-shaped assemblies - gives us insight into\n how the assembly process is occurring. Using stochastic models that\n simulate addition and dissociation of each type of DNA tile, as well\n as simplified models that more cleanly examine the generic phenomena,\n we dissect the contribution of accretion vs aggregation, reversible vs\n irreversible and seeded vs unseeded assumptions for describing the\n growth processes. The results suggest strategies for controlling\n self-assembly to make more uniformly-shaped assemblies.", "date": "2004", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "108-125", "id_number": "CaltechAUTHORS:20110309-104202835", "isbn": "3-540-20930-1", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104202835", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "F30602-012-0561" }, { "agency": "NASA", "grant_number": "NRA2-37143" }, { "agency": "GenTel" } ] }, "contributors": { "items": [ { "id": "Chen-Junghei", "name": { "family": "Chen", "given": "Junghuei" } }, { "id": "Reif-J", "name": { "family": "Reif", "given": "John" } } ] }, "doi": "10.1007/978-3-540-24628-2_12", "primary_object": { "basename": "OneDimBoundaries_DNA9_preprint.pdf", "url": "https://authors.library.caltech.edu/records/1x89h-zdn73/files/OneDimBoundaries_DNA9_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2004", "author_list": "Schulman, Rebecca; Lee, Shaun; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jcvj4-7gn26", "eprint_id": 22768, "eprint_status": "archive", "datestamp": "2023-08-19 12:43:16", "lastmod": "2024-01-13 00:11:02", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Bekbolatov-R", "name": { "family": "Bekbolatov", "given": "Renat" } } ] }, "title": "Proofreading tile sets: Error correction for algorithmic self-assembly", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2004 Springer-Verlag Berlin Heidelberg.\nThis work benefited from discussions with Leonard Adleman, Matthew Cook,\nAshish Gael, Paul Rothemund, Rebecca Schulman, Georg Seelig, David\nSoloveichik, and Chris Umans. Thanks to John Reif for encouraging me\nto write this up and for sharing his unpublished manuscript. EW and\nRB were supported by NSF CAREER Grant No. 0093486, DARPA BioComputation\nContract F30602-01-2-0561, NASA NRA2-37143, and GenTel.\nSimulation code and tile sets used in this paper, as well as MATLAB\nscripts for evaluating the kinetic trapping models, may be obtained from\nhttp://www .dna.caltech.edu/SupplementaryMaterial.\n\nSubmitted - proofreading_DNA9_preprint.pdf
", "abstract": "For robust molecular implementation of tile-based algorithmic\nself-assembly, methods for reducing errors must be developed. Previous\nstudies suggested that by control of physical conditions, such as\ntemperature and the concentration of tiles, errors (\u03b5) can be reduced\nto an arbitrarily low rate - but at the cost of reduced speed (r) for\nthe self-assembly process. For tile sets directly implementing blocked\ncellular automata, it was shown that r \u2248 \u03b2\u03b5^2 was optimal. Here, we\nshow that an improved construction, which we refer to as proofreading\ntile sets, can in principle exploit the cooperativity of tile assembly reactions\nto dramatically improve the scaling behavior to r \u2248 \u03b2\u03b5 and better.\nThis suggests that existing DNA-based molecular tile approaches may be\nimproved to produce macroscopic algorithmic crystals with few errors.\nGeneralizations and limitations of the proofreading tile set construction\nare discussed.", "date": "2004", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "126-144", "id_number": "CaltechAUTHORS:20110309-104203016", "isbn": "3-540-20930-1", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104203016", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CNS-0093486" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "F30602-01-2-0561" }, { "agency": "NASA", "grant_number": "NRA2-37143" }, { "agency": "GenTel" } ] }, "contributors": { "items": [ { "id": "Chen-Junghei", "name": { "family": "Chen", "given": "Junghuei" } }, { "id": "Reif-J", "name": { "family": "Reif", "given": "John" } } ] }, "doi": "10.1007/978-3-540-24628-2_13", "primary_object": { "basename": "proofreading_DNA9_preprint.pdf", "url": "https://authors.library.caltech.edu/records/jcvj4-7gn26/files/proofreading_DNA9_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2004", "author_list": "Winfree, Erik and Bekbolatov, Renat" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fry6p-wqm45", "eprint_id": 22766, "eprint_status": "archive", "datestamp": "2023-08-19 12:42:58", "lastmod": "2024-01-13 00:10:59", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cook-M", "name": { "family": "Cook", "given": "Matthew" } }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Self-assembled circuit patterns", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2004 Springer-Verlag Berlin Heidelberg. \n\nM.C. is supported in part by the \"Alpha Project\" that is funded by a grant from the National Human Genome Research Institute (Grant No. P50 HG02370). P.W.K.R. is supported by a Beckman Postdoctoral Fellowship. E.W. is supported by NSF Career Grant No. 0093486, DARPA BIOCOMP Contract F30602-01-2-0561, and NASA NRA2-37143.\n\nSubmitted - SAcircuits_DNA9_preprint.pdf
", "abstract": "Self-assembly is a process in which basic units aggregate under attractive forces to form larger compound structures. Recent\n theoretical work has shown that pseudo-crystalline self-assembly can be\n algorithmic, in the sense that complex logic can be programmed into the\n growth process [26]. This theoretical work builds on the theory of\n two-dimensional tilings [8], using rigid square tiles called Wang\n tiles [24] for the basic units of self-assembly, and leads to\n Turing-universal models such as the Tile Assembly Model [28]. Using\n the Tile Assembly Model, we show how algorithmic self-assembly can be\n exploited for fabrication tasks such as constructing the patterns that\n define certain digital circuits, including demultiplexers, RAM arrays,\n pseudowavelet transforms, and Hadamard transforms. Since DNA\n self-assembly appears to be promising for implementing the arbitrary\n Wang tiles [30, 13] needed for programming in the Tile Assembly\n Model, algorithmic self-assembly methods such as those presented in\n this paper may eventually become a viable method of arranging molecular\n electronic components [18], such as carbon nanotubes [10, 1], into\n molecular-scale circuits.", "date": "2004", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "91-107", "id_number": "CaltechAUTHORS:20110309-104202667", "isbn": "3-540-20930-1", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104202667", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P50 HG02370" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "NSF", "grant_number": "CCF-0093486" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "F30602-01-2-0561" }, { "agency": "NASA", "grant_number": "NRA2-37143" }, { "agency": "National Human Genome Research Institute" } ] }, "contributors": { "items": [ { "id": "Chen-J", "name": { "family": "Chen", "given": "Junghuei" } }, { "id": "Reif-J", "name": { "family": "Reif", "given": "John" } } ] }, "doi": "10.1007/978-3-540-24628-2_11", "primary_object": { "basename": "SAcircuits_DNA9_preprint.pdf", "url": "https://authors.library.caltech.edu/records/fry6p-wqm45/files/SAcircuits_DNA9_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2004", "author_list": "Cook, Matthew; Rothemund, Paul W. K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b03mj-z4v66", "eprint_id": 27364, "eprint_status": "archive", "datestamp": "2023-08-19 12:35:01", "lastmod": "2023-10-24 17:05:54", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "DNA Computing by Self-Assembly", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2003 National Academy of Engineering.\n\nPublished - FOE_2003_final.pdf
Submitted - FOE_2003_draft.pdf
", "abstract": "Information and algorithms appear to be central to biological organization\nand processes, from the storage and reproduction of genetic information to\nthe control of developmental processes to the sophisticated computations\nperformed by the nervous system. Much as human technology uses electronic\nmicroprocessors to control electromechanical devices, biological\norganisms use biochemical circuits to control molecular and chemical events.\nThe engineering and programming of biochemical circuits, in vivo and in\nvitro, would transform industries that use chemical and nanostructured\nmaterials. Although the construction of biochemical circuits has been\nexplored theoretically since the birth of molecular biology, our practical\nexperience with the capabilities and possible programming of biochemical\nalgorithms is still very young.", "date": "2003-12", "date_type": "published", "publication": "The Bridge", "volume": "33", "number": "4", "publisher": "National Academy of Engineering", "pagerange": "31-38", "id_number": "CaltechAUTHORS:20111024-084902244", "issn": "0737-6278", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-084902244", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "primary_object": { "basename": "FOE_2003_final.pdf", "url": "https://authors.library.caltech.edu/records/b03mj-z4v66/files/FOE_2003_final.pdf" }, "related_objects": [ { "basename": "FOE_2003_draft.pdf", "url": "https://authors.library.caltech.edu/records/b03mj-z4v66/files/FOE_2003_draft.pdf" } ], "resource_type": "article", "pub_year": "2003", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/vyj0c-kqm25", "eprint_id": 27062, "eprint_status": "archive", "datestamp": "2023-08-19 02:55:20", "lastmod": "2023-10-24 16:49:47", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Simulations of Computing by Self-Assembly", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1998 California Institute of Technology.\n\nMay 31, 1998. \n\nI am deeply grateful for stimulating discussions, suggestions, questions, and technical help from John Hopfield, Sanjoy Mahajan, Paul Rothemund, Len Adleman, John Reif, and James Wetmur. All errors, whatever their rate may be, are mine. MATLAB 5.2 code for running the simulations and reproducing all the figures in this paper may be obtained from the author. This work has been supported by the National Institute for Mental Health (Training Grant # 5 T32 MH 19138-07. General Motors' Technology Research Partnerships program, and by the\nCenter for Neuromorphic Systems Engineering as a part of the National Science Foundation Engineering Research Center Program under grant EEC-9402726).\n\nSubmitted - 22.pdf
Submitted - 22.ps
", "abstract": "Winfree (1996) proposed a Turing-universal model of DNA self-assembly. In this abstract model, DNA double-crossover molecules self-assemble to form an algorithmically-patterned two-dimensional lattice. Here, we develop a more realistic model based on the thermodynamics and kinetics of oligonucleotide hydridization. Using a computer simulation, we investigate what physical factors influence the error rates, i.e., when the more realistic model deviates from the ideal of the abstract model. We find, in agreement with rules of thumb for crystal growth, that the lowest error rates occur at the melting temperature when crystal growth is slowest, and that error rates can be made arbitrarily low by decreasing concentration and increasing binding strengths.", "date": "2003-04-16", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechCSTR:1998.22", "official_url": "https://resolver.caltech.edu/CaltechCSTR:1998.22", "rights": "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "5 T32 MH 19138-07" }, { "agency": "General Motors Technology Research Partnerships Program" }, { "agency": "NSF", "grant_number": "EEC-9402726" }, { "agency": "Center for Neuromorphic Systems Engineering, Caltech" } ] }, "local_group": { "items": [ { "id": "Computer-Science-Technical-Reports" } ] }, "doi": "10.7907/Z9TB14X7", "primary_object": { "basename": "22.ps", "url": "https://authors.library.caltech.edu/records/vyj0c-kqm25/files/22.ps" }, "related_objects": [ { "basename": "22.pdf", "url": "https://authors.library.caltech.edu/records/vyj0c-kqm25/files/22.pdf" } ], "resource_type": "monograph", "pub_year": "2003", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qvetx-p0t89", "eprint_id": 27061, "eprint_status": "archive", "datestamp": "2023-08-19 02:23:25", "lastmod": "2023-10-24 16:49:44", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Whiplash PCR for O(1) Computing", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1998 California Institute of Technology.\n\nSubmitted - 23.pdf
Submitted - whiplash-TR1998-23.ps
", "abstract": "This paper reviews the experimental technique of whiplash PCR, as introduced in Hagiya et al. (in press), and proposes a model of computation based on this technique in combination with assembly PCR (Stemmer et al. 1995). In this model, based on GOTO graphs, a number of NP-complete problems can be solved in O(1) biosteps, including branching program satisfiability, the independent set problem, and the Hamiltonian path problem. In addition, we propose a simple extension of the experimental technique that allows single DNA strands to simulate the execution of a feed-forward circuit, giving rise to a solution to the circuit satisfiability problem in O(1) biosteps.", "date": "2003-04-16", "date_type": "published", "publisher": "California Institute of Technology", "id_number": "CaltechCSTR:1998.23", "official_url": "https://resolver.caltech.edu/CaltechCSTR:1998.23", "rights": "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.", "local_group": { "items": [ { "id": "Computer-Science-Technical-Reports" } ] }, "doi": "10.7907/Z94M92KH", "primary_object": { "basename": "23.pdf", "url": "https://authors.library.caltech.edu/records/qvetx-p0t89/files/23.pdf" }, "related_objects": [ { "basename": "whiplash-TR1998-23.ps", "url": "https://authors.library.caltech.edu/records/qvetx-p0t89/files/whiplash-TR1998-23.ps" } ], "resource_type": "monograph", "pub_year": "2003", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1hjmr-84k83", "eprint_id": 3650, "eprint_status": "archive", "datestamp": "2023-08-21 23:43:07", "lastmod": "2023-10-23 15:57:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Protein Design is NP-hard", "ispublished": "pub", "full_text_status": "public", "keywords": "complexity/design/NP-complete/NP-hard/proteins", "note": "\u00a9 2002 Oxford University Press. Reprinted with permission. \n\nReceived March 13, 2002; revised May 31, 2002; accepted July 2, 2002. \n\nWe thank L.J. Schulman for a critical reading of the manuscript. This research was supported by the Burroughs-Wellcome Foundation through the Caltech Initiative in Computational Molecular Biology (NAP) and by the Defense Advanced Research Projects Agency (DARPA) and Air Force Research Laboratory under agreement F30602-010200561 (both authors).\n\nPublished - PIEpeds02.pdf
", "abstract": "Biologists working in the area of computational protein design have never doubted the seriousness of the algorithmic challenges that face them in attempting in silico sequence selection. It turns out that in the language of the computer science community, this discrete optimization problem is NP-hard. The purpose of this paper is to explain the context of this observation, to provide a simple illustrative proof and to discuss the implications for future progress on algorithms for computational protein design.", "date": "2002-10", "date_type": "published", "publication": "Protein Engineering", "volume": "15", "number": "10", "publisher": "Oxford University Press", "pagerange": "779-782", "id_number": "CaltechAUTHORS:PIEpeds02.939", "issn": "0269-2139", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:PIEpeds02.939", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Burroughs-Wellcome Foundation" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Air Force Research Laboratory", "grant_number": "F30602-010200561" }, { "agency": "Caltech Initiative in Computational Molecular Biology" } ] }, "doi": "10.1093/protein/15.10.779", "primary_object": { "basename": "PIEpeds02.pdf", "url": "https://authors.library.caltech.edu/records/1hjmr-84k83/files/PIEpeds02.pdf" }, "resource_type": "article", "pub_year": "2002", "author_list": "Pierce, Niles A. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/e6kwb-kqg74", "eprint_id": 103149, "eprint_status": "archive", "datestamp": "2023-08-21 22:54:39", "lastmod": "2024-01-15 03:02:07", "type": "book", "metadata_visibility": "show", "creators": { "items": [ { "name": { "family": "Landweber", "given": "Laura F." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Evolution as Computation", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Algorithms; evolution; genetic algorithm; genetic algorithms; genome; mutation; optimization; the origin", "note": "\u00a9 2002 Springer-Verlag Berlin Heidelberg.", "abstract": "The study of the genetic basis for evolution has flourished in this century, as well as our understanding of the evolvability and programmability of biological systems. Genetic algorithms meanwhile grew out of the realization that a computer program could use the biologically-inspired processes of mutation, recombination, and selection to solve hard optimization problems. Genetic and evolutionary programming provide further approaches to a wide variety of computational problems. A synthesis of these experiences reveals fundamental insights into both the computational nature of biological evolution and processes of importance to computer science. Topics include biological models of nucleic acid information processing and genome evolution; molecules, cells, and metabolic circuits that compute logical relationships; the origin and evolution of the genetic code; and the interface with genetic algorithms, genetic and evolutionary programming. This research combines theory and experiments to understand the computations that take place in cells and the combinatorial processes that drive evolution at the molecular level.", "date": "2002", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "id_number": "CaltechAUTHORS:20200512-134206543", "isbn": "978-3-642-63081-1", "book_title": "Evolution as Computation", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200512-134206543", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Landweber-L-F", "name": { "family": "Landweber", "given": "Laura F." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" } } ] }, "doi": "10.1007/978-3-642-55606-7", "resource_type": "book", "pub_year": "2002", "author_list": "Landweber, Laura F. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fkkm8-xz342", "eprint_id": 22770, "eprint_status": "archive", "datestamp": "2023-08-19 08:43:59", "lastmod": "2024-01-13 00:11:04", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Landweber-Laura-F", "name": { "family": "Landweber", "given": "Laura F." } } ] }, "title": "Introduction: Evolution and Computation: Where Do They Meet?", "ispublished": "unpub", "full_text_status": "public", "note": "[introduction included in front matter]", "abstract": "Evolutionary algorithms originated in the 1970s from the realization that computer programs can use the biologically inspired processes of genetic mutation, recombination, and selection to solve optimization problems that are analytically intractable. Successful applications to a wider gamut of problems became possible with the addition of new mechanisms such as generalized recombination, gene duplication, \"developmental\" evaluation of genomes, and unbounded genome size. Has this experience distilled concepts of importance for understanding biological evolution?", "date": "2002", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin, Germany", "pagerange": "v-ix", "id_number": "CaltechAUTHORS:20110309-104203989", "isbn": "978-3-642-63081-1", "book_title": "Evolution as Computation: DIMACS Workshop, Princeton, January 1999", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104203989", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Landweber-Laura-F", "name": { "family": "Landweber", "given": "Laura F." } } ] }, "resource_type": "book_section", "pub_year": "2002", "author_list": "Winfree, Erik and Landweber, Laura F." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cvc8r-5v978", "eprint_id": 104934, "eprint_status": "archive", "datestamp": "2023-08-21 21:53:36", "lastmod": "2024-01-15 17:04:18", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "In Vitro Transcriptional Circuits", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "Intelligent Machine; Recurrent Neural Network; Digital Circuit; Ring Oscillator; Drosophila Embryo", "note": "\u00a9 2001 Springer-Verlag London.", "abstract": "The structural similarity of neural networks and genetic regulatory networks to digital circuits, and hence to each other, was noted from the very beginning of their study [7,5]. Generic properties of both types of network have been analyzed using the same class of abstract models [3]. The same rate equations proposed for recurrent neural networks [4] have been used, with a few embellishments, to model genetic regulatory circuits controlling development of Drosophila embryos [6]. However, whereas research in neural networks has a long history of both analytic approaches, aimed at understanding the brain, and synthetic approaches, aimed at creating intelligent machines, research in genetic regulatory networks has been entirely analytic prior to very recent work implementing small synthetic genetic regulatory networks in E. Coli [8, 1, 2]. Although genetic regulatory systems are not fast, they are small; E. coli is one cubic micron yet it contains thousands of regulated genes.", "date": "2001", "date_type": "published", "publisher": "Springer", "place_of_pub": "London", "pagerange": "121-122", "id_number": "CaltechAUTHORS:20200812-123245128", "isbn": "978-1-85233-415-4", "book_title": "Unconventional Models of Computation, UMC'2K", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200812-123245128", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Antoniou-I", "name": { "family": "Antoniou", "given": "I." } }, { "id": "Calude-C-S", "name": { "family": "Calude", "given": "C. S." } }, { "id": "Dinneen-M-J", "name": { "family": "Dinneen", "given": "M. J." } } ] }, "doi": "10.1007/978-1-4471-0313-4_10", "resource_type": "book_section", "pub_year": "2001", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k0gxw-cqs09", "eprint_id": 27367, "eprint_status": "archive", "datestamp": "2023-08-21 21:48:37", "lastmod": "2024-01-13 05:44:00", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Eng-T", "name": { "family": "Eng", "given": "Tony" } }, { "id": "Rozenberg-G", "name": { "family": "Rozenberg", "given": "Grzegorz" } } ] }, "title": "String tile models for DNA computing by self-assembly", "ispublished": "unpub", "full_text_status": "public", "keywords": "Turing Machine; Maximal Assembly; Maximal Path; General Tile; Planar Tile", "note": "\u00a9 2001 Springer-Verlag Berlin Heidelberg. \n\nThe authors are indebted to Joost Engelfriet and Hendrik\nJan Hoogeboom for their guidance through the maze of results on the output languages of various sorts of \ntransducers, and to John Reif and Thorn LaBean\nfor their critical reading, discussion, and encouragement.\n\nSubmitted - stringtiles_preprint.pdf
", "abstract": "This paper investigates computation by linear assemblies of complex DNA tiles, which we call string tiles. By keeping track of the strands as they weave back and forth through the assembly, we show that surprisingly sophisticated calculations can be performed using linear self-assembly. Examples range from generating an addition table to providing O(1) solutions to CNF-SAT and DHPP. We classify the families of languages that can be generated by various types of DNA molecules, and establish a correspondence to the existing classes ET0L_(ml) and ET0L_(fin). Thus, linear self-assembly of string tiles can generate the output languages of finite-visit Turing Machines.", "date": "2001", "date_type": "published", "publisher": "Springer", "place_of_pub": "Berlin", "pagerange": "63-88", "id_number": "CaltechAUTHORS:20111024-092612665", "isbn": "978-3-540-42076-7", "book_title": "DNA Computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-092612665", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Condon-A", "name": { "family": "Condon", "given": "Anne" } } ] }, "doi": "10.1007/3-540-44992-2_6", "primary_object": { "basename": "stringtiles_preprint.pdf", "url": "https://authors.library.caltech.edu/records/k0gxw-cqs09/files/stringtiles_preprint.pdf" }, "resource_type": "book_section", "pub_year": "2001", "author_list": "Winfree, Erik; Eng, Tony; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7b16h-n9g10", "eprint_id": 22774, "eprint_status": "archive", "datestamp": "2023-08-19 05:41:34", "lastmod": "2023-10-23 17:11:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Algorithmic Self-Assembly of DNA: Theoretical Motivations and 2D Assembly Experiments", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2000 Adenine Press.\n\n\nThis work would have been impossible without the sage advise\nof my thesis advisor, John Hopfield. John Abelson welcomed me\ninto his laboratory, where this work was done. Ned Seeman\ntaught me experimental science and gave me generous technical\nand conceptual advice on this project from its inception. Thanks\nto Anca Segall, Ely Rabani, and Bob Moision for instruction and\nadvice on AFM imaging, and to the Beckman Institute\nMolecular Materials resource center for assistance and use of\ntheir AFM facilities. I also thank Paul Rothemund, Hui Wang,\nLen Adleman, John Reif, and many others whose discussions\nhave been invaluable and inspirational. Computer models of the\nDX molecules used in this study, shown in Figure 6, were generated\nusing NAMOT2 (Carter and Tung 96).\n\nPublished - algSA_JBSD.pdf
", "abstract": "Biology makes things far smaller and more complex than anything produced by human engineering. The biotechnology revolution has for the first time given us the tools necessary to consider engineering on the molecular level. Research in DNA computation, launched by Len Adleman, has opened the door for experimental study of programmable biochemical reactions. Here we focus on a single biochemical mechanism, the self-assembly of DNA structures, that is theoretically sufficient for Turing-universal computation. The theory combines Hao Wang?s purely mathematical Tiling Problem with the branched DNA constructions of Ned Seeman. In the context of mathematical logic, Wang showed how jigsaw-shaped tiles can be designed to simulate the operation of any Turing Machine. For a biochemical implementation, we will need molecular Wang tiles. DNA molecular structures and intermolecular interactions are particularly amenable to design and are sufficient for the creation of complex molecular objects. The structure of individual molecules can be designed by maximizing desired and minimizing undesired Watson-Crick complementarity. Intermolecular interactions are programmed by the design of sticky ends that determine which molecules associate, and how. The theory has been demonstrated experimentally using a system of synthetic DNA double-crossover molecules that self-assemble into two-dimensional crystals that have been visualized by atomic force microscopy. This experimental system provides an excellent platform for exploring the relationship between computation and molecular self-assembly, and thus represents a first step toward the ability to program molecular reactions and molecular structures.", "date": "2000-05", "date_type": "published", "publication": "Journal of Biomolecular Structure and Dynamics", "volume": "11", "number": "2", "publisher": "Adenine Press", "pagerange": "263-270", "id_number": "CaltechAUTHORS:20110309-104204682", "issn": "0739-1102", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104204682", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "primary_object": { "basename": "algSA_JBSD.pdf", "url": "https://authors.library.caltech.edu/records/7b16h-n9g10/files/algSA_JBSD.pdf" }, "resource_type": "article", "pub_year": "2000", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/j28t5-3v273", "eprint_id": 72795, "eprint_status": "archive", "datestamp": "2023-08-19 05:43:01", "lastmod": "2023-10-23 22:57:24", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "The program-size complexity of self-assembled squares", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2000 ACM.", "abstract": "Molecular self-assembly gives rise to a great diversity of complex forms, from crystals and DNA helices to microtubules\nand holoenzymes. We study a formal model of pseudocrystalline self-assembly, called the Tile Assembly Model, in which a tile may be added to the growing object when the total interaction strength with its neighbors exceeds a parameter \u03a4. This model has been shown to be Turing-universal. Thus, self-assembled objects can be studied from the point of view of computational complexity. Here, we define the program size complexity of an NxN square to be the minimum number of distinct tiles required to self-assemble the square and no other objects. We study this complexity under the Tile Assembly Model and find a dramatic decrease in complexity, from N^2 tiles to O(log N) tiles, as \u03a4 is increased from 1 (where bonding is noncooperative) to 2 (allowing cooperative bonding). Further, we find that the size of the largest square uniquely produced by a set of n\ntiles grows faster than any computable function.", "date": "2000-05", "date_type": "published", "publisher": "ACM", "place_of_pub": "New York, NY", "pagerange": "459-468", "id_number": "CaltechAUTHORS:20161213-162052032", "isbn": "1-58113-184-4", "book_title": "STOC '00 Proceedings of the thirty-second annual ACM symposium on Theory of computing", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161213-162052032", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Yao-Frances", "name": { "family": "Yao", "given": "Frances" } }, { "id": "Luks-E", "name": { "family": "Luks", "given": "Eugene" } } ] }, "doi": "10.1145/335305.335358", "resource_type": "book_section", "pub_year": "2000", "author_list": "Rothemund, Paul W. K. and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1p8vn-myj41", "eprint_id": 22775, "eprint_status": "archive", "datestamp": "2023-08-19 05:28:57", "lastmod": "2023-10-23 17:11:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "LaBean-T-H", "name": { "family": "LaBean", "given": "Thomas H." } }, { "id": "Yan-Hao", "name": { "family": "Yan", "given": "Hao" } }, { "id": "Kopatsch-J", "name": { "family": "Kopatsch", "given": "Jens" } }, { "id": "Liu-Furong", "name": { "family": "Liu", "given": "Furong" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Reif-J-H", "name": { "family": "Reif", "given": "John H." } }, { "id": "Seeman-N-C", "name": { "family": "Seeman", "given": "Nadrian C." }, "orcid": "0000-0002-9680-4649" } ] }, "title": "Construction, analysis, ligation, and self-assembly of DNA triple crossover complexes", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2000 American Chemical Society. \n\nReceived September 20, 1999. Published on Web 02/09/2000. \n\nWe thank Dr. Brad Chaires for useful advice about DNA melting experiments. This work has been supported by grants NSF-CCR-97-25021 and CCR-96-33567 from DARPA and the National Science Foundation to J.H.R. and N.C.S., IRI-9619647 from NSF to J.H.R., ARO contract DAAH-0496-1-0448 to J.H.R., N00014-89-J-3078 from the Office of Naval Research to N.C.S., GM-29554 from the National Institute of General Medical Sciences to N.C.S., and F30602-98-C-0148 from the Air Force Research Laboratory Located at Rome, NY, to N.C.S.", "abstract": "This paper extends the study and prototyping of unusual DNA motifs, unknown in nature, but founded\non principles derived from biological structures. Artificially designed DNA complexes show promise as building\nblocks for the construction of useful nanoscale structures, devices, and computers. The DNA triple crossover\n(TX) complex described here extends the set of experimentally characterized building blocks. It consists of\nfour oligonucleotides hybridized to form three double-stranded DNA helices lying in a plane and linked by\nstrand exchange at four immobile crossover points. The topology selected for this TX molecule allows for the\npresence of reporter strands along the molecular diagonal that can be used to relate the inputs and outputs of\nDNA-based computation. Nucleotide sequence design for the synthetic strands was assisted by the application\nof algorithms that minimize possible alternative base-pairing structures. Synthetic oligonucleotides were purified,\nstoichiometric mixtures were annealed by slow cooling, and the resulting DNA structures were analyzed by\nnondenaturing gel electrophoresis and heat-induced unfolding. Ferguson analysis and hydroxyl radical\nautofootprinting provide strong evidence for the assembly of the strands to the target TX structure. Ligation\nof reporter strands has been demonstrated with this motif, as well as the self-assembly of hydrogen-bonded\ntwo-dimensional crystals in two different arrangements. Future applications of TX units include the construction\nof larger structures from multiple TX units, and DNA-based computation. In addition to the presence of reporter\nstrands, potential advantages of TX units over other DNA structures include space for gaps in molecular arrays,\nlarger spatial displacements in nanodevices, and the incorporation of well-structured out-of-plane components\nin two-dimensional arrays.", "date": "2000-03-08", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "122", "number": "9", "publisher": "American Chemical Society", "pagerange": "1848-1860", "id_number": "CaltechAUTHORS:20110309-104204822", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104204822", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCR-97-25021" }, { "agency": "NS", "grant_number": "CCR-96-33567" }, { "agency": "NSF", "grant_number": "IRI-9619647" }, { "agency": "Army Research Office (ARO)", "grant_number": "DAAH-0496-1-0448" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-89-J-3078" }, { "agency": "NIH", "grant_number": "GM-29554" }, { "agency": "Air Force Research Laboratory", "grant_number": "F30602-98-C-0148" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" } ] }, "doi": "10.1021/ja993393e", "resource_type": "article", "pub_year": "2000", "author_list": "LaBean, Thomas H.; Yan, Hao; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1dgyt-fev23", "eprint_id": 27569, "eprint_status": "archive", "datestamp": "2023-08-19 05:03:20", "lastmod": "2024-01-13 05:45:34", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Kevin-Bio", "name": { "family": "Chen", "given": "Kevin" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Error Correction in DNA Computing: Misclassification and\n Strand Loss", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2000 American Mathematical Society.\n\nPublished - Error_Correction.pdf
", "abstract": "We present a method of transforming an extract-based DNA computation that is error-prone into one that is relatively error-free. These improvements in error rates are achieved without the supposition of any improvements in the reliability of the underlying laboratory techniques. We assume that only two types of errors are possible: a DNA strand may be incorrectly processed or it may be lost entirely. We show to deal with each of these\nerrors individually and then analyze the tradeoff when both must be optimized simultaneously.", "date": "2000", "date_type": "published", "publisher": "American Mathematical Society", "place_of_pub": "Providence, RI", "pagerange": "49-63", "id_number": "CaltechAUTHORS:20111102-073137217", "isbn": "9780821820537", "book_title": "DNA Based Computers V", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111102-073137217", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" } }, { "id": "Gifford-D-K", "name": { "family": "Gifford", "given": "David K." } } ] }, "primary_object": { "basename": "Error_Correction.pdf", "url": "https://authors.library.caltech.edu/records/1dgyt-fev23/files/Error_Correction.pdf" }, "resource_type": "book_section", "pub_year": "2000", "author_list": "Chen, Kevin and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pqzf3-d3r39", "eprint_id": 27564, "eprint_status": "archive", "datestamp": "2023-08-19 05:03:15", "lastmod": "2023-10-24 17:15:00", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "LaBean-T-H", "name": { "family": "LaBean", "given": "Thomas H." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Reif-J-H", "name": { "family": "Reif", "given": "John H." } } ] }, "title": "Experimental Progress in Computation by Self-Assembly of DNA Tilings", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2000 American Mathematical Society.\nWe wish to sincerely thank: Ned Seeman and Hao Yan for their considerable\nand invaluable roles in construction and analysis of the TAO tile; Tony Eng\nand Grzegorz Rosenberg for development and enlightening discussion of string tile\nconcepts; and Wolfgang Frey and Ashutosh Chilkoti for assistance with atomic\nforce microscopy. This work was supported in part by Grants NSF/DARPA CCR-9725021, CCR-96-33567, NSF IRI-9619647, ARO contract DAAH-04-96-1-0448, and ONR contract N00014-99-1-0406.\n\nPublished - Experimental_Progress.pdf
", "abstract": "Approaches to DNA-based computing by self-assembly require the\nuse of D. T A nanostructures, called tiles, that have efficient chemistries, expressive\ncomputational power: and convenient input and output (I/O) mechanisms.\nWe have designed two new classes of DNA tiles: TAO and TAE, both\nof which contain three double-helices linked by strand exchange. Structural\nanalysis of a TAO molecule has shown that the molecule assembles efficiently\nfrom its four component strands. Here we demonstrate a novel method for\nI/O whereby multiple tiles assemble around a single-stranded (input) scaffold\nstrand. Computation by tiling theoretically results in the formation of structures\nthat contain single-stranded (output) reported strands, which can then\nbe isolated for subsequent steps of computation if necessary. We illustrate the\nadvantages of TAO and TAE designs by detailing two examples of massively\nparallel arithmetic: construction of complete XOR and addition tables by linear\nassemblies of DNA tiles. The three helix structures provide flexibility for\ntopological routing of strands in the computation: allowing the implementation\nof string tile models.", "date": "2000", "date_type": "published", "publisher": "American Mathematical Society", "place_of_pub": "Providence, RI", "pagerange": "123-40", "id_number": "CaltechAUTHORS:20111101-150157119", "isbn": "9780821820537", "book_title": "DNA Based Computers V", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111101-150157119", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF/Defense Advanced Research Projects Agency (DARPA)", "grant_number": "CCR-9725021" }, { "agency": "NSF/Defense Advanced Research Projects Agency (DARPA)", "grant_number": "CCR-96-33567" }, { "agency": "NSF", "grant_number": "IRI-9619647" }, { "agency": "Army Research Office (ARO)", "grant_number": "DAAH-04-96-1-0448" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-99-1-0406" } ] }, "contributors": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" } }, { "id": "Gifford-D-K", "name": { "family": "Gifford", "given": "David K." } } ] }, "primary_object": { "basename": "Experimental_Progress.pdf", "url": "https://authors.library.caltech.edu/records/pqzf3-d3r39/files/Experimental_Progress.pdf" }, "resource_type": "book_section", "pub_year": "2000", "author_list": "LaBean, Thomas H.; Winfree, Erik; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/v456j-vk915", "eprint_id": 27366, "eprint_status": "archive", "datestamp": "2023-08-19 05:03:10", "lastmod": "2023-10-24 17:06:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Seeman-N-C", "name": { "family": "Seeman", "given": "Nadrian C." }, "orcid": "0000-0002-9680-4649" }, { "id": "Liu-Furong", "name": { "family": "Liu", "given": "Furong" } }, { "id": "Mao-Chengde", "name": { "family": "Mao", "given": "Chengde" }, "orcid": "0000-0001-7516-8666" }, { "id": "Yang-Xiaoping", "name": { "family": "Yang", "given": "Xiaoping" } }, { "id": "Wenzler-L-A", "name": { "family": "Wenzler", "given": "Lisa A." } }, { "id": "Sha-R", "name": { "family": "Sha", "given": "Ruojie" } }, { "id": "Sun-Weiqiong", "name": { "family": "Sun", "given": "Weiqiong" } }, { "id": "Shen-Zhiyong", "name": { "family": "Shen", "given": "Zhiyong" } }, { "id": "Li-Xiaojun", "name": { "family": "Li", "given": "Xiaojun" } }, { "id": "Qi-Jing", "name": { "family": "Qi", "given": "Jing" } }, { "id": "Zhang-Yuwen", "name": { "family": "Zhang", "given": "Yuwen" } }, { "id": "Fu-Tsu-Ju", "name": { "family": "Fu", "given": "Tsu-Ju" } }, { "id": "Chen-Junghei", "name": { "family": "Chen", "given": "Junghuei" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Two Dimensions and Two States in DNA Nanotechnology", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2000 Adenine Press.\nThis work has been supported by grants GM-29554 from the\nNational Institute of General Medical Sciences, N00014-89-J-\n3078 from the Office of Naval Research, NSF-CCR-97-25021\nfrom DARPA/National Science Foundation and F30602-98-C-\n0148 from the Information Directorate of the Rome NY Air\nForce Research Laboratory to N.C.S., by Margaret and Herman\nSokol Fellowships to J.C. and X.Y., and by NYU-GSAS\nDissertation Fellowships to Y.Z. and C.M.\n\nPublished - TwoDimTwoStates.pdf
", "abstract": "The construction of periodic matter and nanomechanical devices are central goals of DNA\nnanotechnology. The minimal requirements for components of designed crystals are [1] programmable\ninteractions, [2] predictable local intermolecular structures and [3] rigidity. The\nsticky-ended association of DNA molecules fulfills the first two criteria, because it is specific\nand diverse, and it results in the formation of B-DNA. Stable branched DNA molecules\npermit the formation of networks, but individual single branches are too flexible. Antiparallel\nDNA double crossover (DX) molecules can provide the necessary rigidity, so we use these\ncomponents to tile the plane. It is possible to include DNA hairpins that act as topographic\nlabels for this 2-D crystalline array, because they protrude from its plane. By altering sticky\nends, it is possible to change the topographic features formed by these hairpins, and to detect\nthese changes by means of AFM. We can modify arrays by restricting hairpins or by adding\nthem to sticking ends protruding from the array.\nAlthough individual branched junctions are unsuitable for use as crystalline components, parallelograms\nof four 4-arm junction molecules are sufficiently rigid that they can be used to\nproduce 2D arrays. The arrays contain cavities whose dimensions are readily tuned by changing\nthe edges of their parallelogram components. We have used these arrays to measure\ndirectly the angle between the helices of the Holliday junction.\nThe rigidity of the DX motif can also be exploited to produce a nanomechanical device predicated\non the B-Z transition. Two DNA double crossover molecules have been joined by a segment of\nDNA capable of undergoing the B-Z transition. In the B-conformation, the unconnected helices\nof the two molecules are on the same side of the connecting helix, whereas in the Z conformation\nthey are on opposite sides, leading to movements of as much as 60\u00c5. This effect is shown\nby fluorescence resonance energy transfer, because dyes attached to the unconnected helices\nhave different separations in the two states.", "date": "2000", "date_type": "published", "publication": "Journal of Biomolecular Structure and Dynamics", "volume": "11", "number": "S2", "publisher": "Adenine Press", "pagerange": "253-262", "id_number": "CaltechAUTHORS:20111024-091114335", "issn": "0739-1102", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-091114335", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "GM-29554" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-89-J-3078" }, { "agency": "NSF", "grant_number": "CCR-97-25021" }, { "agency": "Rome NY Air Force Research Laboratory Information Directorate", "grant_number": "F30602-98-C-0148" }, { "agency": "Margaret and Herman Sokol Fellowships" }, { "agency": "NYU-GSAS Dissertation Fellowships" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" } ] }, "primary_object": { "basename": "TwoDimTwoStates.pdf", "url": "https://authors.library.caltech.edu/records/v456j-vk915/files/TwoDimTwoStates.pdf" }, "resource_type": "article", "pub_year": "2000", "author_list": "Seeman, Nadrian C.; Liu, Furong; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k3dhm-a5g05", "eprint_id": 22777, "eprint_status": "archive", "datestamp": "2023-08-22 13:46:32", "lastmod": "2023-10-23 17:11:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Adleman-L-M", "name": { "family": "Adleman", "given": "Leonard M." } }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Roweis-S", "name": { "family": "Roweis", "given": "Sam" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "On Applying Molecular Computation to the Data Encryption Standard", "ispublished": "pub", "full_text_status": "public", "keywords": "DES; DNA computation; molecular computation; sticker model", "note": "\u00a9 1999 Mary Ann Liebert, Inc.\nReceived for publication November 9, 1997; accepted as revised October 18, 1998.\nL.M.A. and P.W.K.R. are supported in part by the National Science Foundation under grant CCR-9403662\nand the Sloan Foundation. S.R. is supported in part by the Center for Neuromorphic Systems Engineering as a\npart of the National Science Foundation Engineering Research Center Program under grant EEC-9402726 and\nby the Natural Sciences and Engineering Research Council of Canada. E.W. is supported in part by National\nInstitute for Mental Health (NIMH) training grant no. 5 T32 MH 19138-06 and also by General Motors'\nTechnology Research Partnerships program.\n\nPublished - Stickers_DES1999.pdf
Submitted - des_1_.pdf
", "abstract": "Recently, Boneh, Dunworth, and Lipton (1996) described the potential use of molecular computation in attacking the United States Data\n Encryption Standard (DES), Here, we provide a description of such an\n attack using the sticker model of molecular computation. Our analysis\n suggests that such an attack might be mounted on a tabletop machine\n using approximately a gram of DNA and might succeed even in the\n presence of a large number of errors.", "date": "1999-05-07", "date_type": "published", "publication": "Journal of Computational Biology", "volume": "6", "number": "1", "publisher": "Mary Ann Liebert, Inc.", "pagerange": "53-63", "id_number": "CaltechAUTHORS:20110309-104205166", "issn": "1066-5277", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104205166", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CCR-9403662" }, { "agency": "Alfred P. Sloan Foundation" }, { "agency": "NSF", "grant_number": "EEC-9402726" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "National Institute for Mental Health (NIMH)", "grant_number": "5 T32 MH 19138-06" }, { "agency": "General Motors Technology Research Partnership Program" } ] }, "doi": "10.1089/cmb.1999.6.53", "primary_object": { "basename": "Stickers_DES1999.pdf", "url": "https://authors.library.caltech.edu/records/k3dhm-a5g05/files/Stickers_DES1999.pdf" }, "related_objects": [ { "basename": "des_1_.pdf", "url": "https://authors.library.caltech.edu/records/k3dhm-a5g05/files/des_1_.pdf" } ], "resource_type": "article", "pub_year": "1999", "author_list": "Adleman, Leonard M.; Rothemund, Paul W. K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1jc9b-st552", "eprint_id": 22778, "eprint_status": "archive", "datestamp": "2023-08-22 13:46:37", "lastmod": "2023-10-23 17:11:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Roweis-S", "name": { "family": "Roweis", "given": "Sam" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "On the Reduction of Errors in DNA Computation", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA computations; error reduction; errors; molecular computation", "note": "\u00a9 1999 Mary Ann Liebert, Inc.\nReceived for publication November 9, 1997; accepted as revised December 13, 1998.\nWe would like to express our appreciation to Professor John Baldeschwieler for his contributions to this\npaper through early discussions of this work. We are also grateful to our advisor, Professor John Hopfield,\nfor his perpetual wisdom and long-term advice. A preliminary version of this paper previously appeared as\nSection 5 of Roweis et at. (1998a). The MATLAB code used to generate all the figures in this paper is also\navailable by request from roweis@cns.cattech.edu. S.R. is supported in part by the Center for Neuromorphic\nSystems Engineering as a part of the National Science Foundation Engineering Research Center Program\nunder grant EEC-9402726 and by the Natural Sciences and Engineering Research Council of Canada. E.W.\nis supported in part by National Institute for Mental Health (NIMH) training grant no. 5 T32 MH 19l38-06\nand also by General Motors' Technology Research Partnership program.\n\nPublished - Stickers_errors1999.pdf
", "abstract": "In this paper, we discuss techniques for reducing errors in DNA computation. We investigate several methods for achieving acceptable overall error rates for a computation using basic operations that are error prone. We analyze a single essential biotechnology, sequence-specific separation, and show that separation errors theoretically can be reduced to tolerable levels by invoking a tradeoff between time, space, and error rates at the level of algorithm design. These tradeoffs do not depend upon improvement of the underlying biotechnology which implements the separation step. We outline several specific ways in which error reduction can be done and present numerical calculations of their performance.", "date": "1999-05-07", "date_type": "published", "publication": "Journal of Computational Biology", "volume": "6", "number": "1", "publisher": "Mary Ann Liebert, Inc.", "pagerange": "65-75", "id_number": "CaltechAUTHORS:20110309-104205331", "issn": "1066-5277", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104205331", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Engineering Research Center Program", "grant_number": "EEC-9402726" }, { "agency": "Natural Sciences and Engineering Research Council of Canada" }, { "agency": "National Institute for Mental Health (NIMH)", "grant_number": "5 T32 MH 19l38-06" }, { "agency": "General Motors' Technology Research Partnership Program" } ] }, "doi": "10.1089/cmb.1999.6.65", "primary_object": { "basename": "Stickers_errors1999.pdf", "url": "https://authors.library.caltech.edu/records/1jc9b-st552/files/Stickers_errors1999.pdf" }, "resource_type": "article", "pub_year": "1999", "author_list": "Roweis, Sam and Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/v13f7-b7211", "eprint_id": 27378, "eprint_status": "archive", "datestamp": "2023-08-19 03:40:46", "lastmod": "2024-01-13 05:44:02", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Yang-Xiaoping", "name": { "family": "Yang", "given": "Xiaoping" } }, { "id": "Seeman-N-C", "name": { "family": "Seeman", "given": "Nadrian C." }, "orcid": "0000-0002-9680-4649" } ] }, "title": "Universal Computation via Self-assembly of DNA: Some Theory and Experiments", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1999 American Mathematical Society.\nE. Winfree has been supported in part\nby National Institute for Mental Health (NIMH) Training Grant # 5 T32 MH 19138-06; also by\nGeneral Motors' Technology Research Partnerships program and by the Center for Neuromorphic\nSystems Engineering as a part of the National Science Foundation Engineering Research Center\nProgram under grant EEC-9402726. The experimental portion of this research has been partially\nsupported by grants N00014-89-J-3078 from the Office of Naval Research and GM-29554 from the\nNIH (to NCS).\n\nErik Winfree is grateful to the many people who have helped make his foray into\nthe world of molecules possible, enjoyable, and exciting; special thanks go to Len\nAdleman, Paul Rothemund, Sam Roweis, Dan Abrahams-Gessel, John Hopfield,\nand John Abelson who generously provided laboratory facilities at Caltech for some\nof the experiments reported here.\n\nPublished - Universal_Computation.pdf
Submitted - self-assem_preprint.pdf
", "abstract": "In this paper we examine the computational capabilities inherent in the hybridization of DNA molecules. First we consider theoretical models, and show that the self-assembly of oligonucleotides into linear duplex DNA can\nonly generate sets of sequences equivalent to regular languages. If branched DNA is used for self-assembly of dendrimer structures, only sets of sequences equivalent to context-free languages can be achieved. In contrast, the self-assembly of double crossover molecules into two dimensional sheets or three dimensional solids is theoretically capable of universal computation. The proof\nrelies on a very direct simulation of a universal class of cellular automata. In the second part of this paper, we present results from preliminary experiments which investigate the critical computational step in a two-dimensional self-assembly process.", "date": "1999", "date_type": "published", "publisher": "American Mathematical Society", "place_of_pub": "Providence, RI", "pagerange": "191-213", "id_number": "CaltechAUTHORS:20111024-101156919", "isbn": "0821807560", "book_title": "DNA Based Computers II", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-101156919", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "5 T32 MH 19138-06" }, { "agency": "General Motors Technology Research Partnerships Program" }, { "agency": "NSF", "grant_number": "EEC-9402726" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-89-J-3078" }, { "agency": "NIH", "grant_number": "GM-29554" } ] }, "contributors": { "items": [ { "id": "Landweber-L-F", "name": { "family": "Landweber", "given": "Laura F." } }, { "id": "Baum-E-B", "name": { "family": "Baum", "given": "Eric B." } } ] }, "primary_object": { "basename": "Universal_Computation.pdf", "url": "https://authors.library.caltech.edu/records/v13f7-b7211/files/Universal_Computation.pdf" }, "related_objects": [ { "basename": "self-assem_preprint.pdf", "url": "https://authors.library.caltech.edu/records/v13f7-b7211/files/self-assem_preprint.pdf" } ], "resource_type": "book_section", "pub_year": "1999", "author_list": "Winfree, Erik; Yang, Xiaoping; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/snfgz-51t15", "eprint_id": 22780, "eprint_status": "archive", "datestamp": "2023-08-19 03:13:24", "lastmod": "2023-10-23 17:11:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Liu-F", "name": { "family": "Liu", "given": "Furong" } }, { "id": "Wenzler-L-A", "name": { "family": "Wenzler", "given": "Lisa A." } }, { "id": "Seeman-N-C", "name": { "family": "Seeman", "given": "Nadrian C." }, "orcid": "0000-0002-9680-4649" } ] }, "title": "Design and self-assembly of two-dimensional DNA crystals", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 1998 Nature Publishing Group. \n\nReceived 10 March 1998; Accepted 5 May 1998. \n\nWe thank J. Hopfield, S. Roweis, S. Mahajan, C. Brody, L. Adleman and P. Rothemund for discussion; J. Abelson and his group for use of his laboratory and for technical advice; A. Segal, E. Rabani and R. Moision for instruction and advice on AFM imaging; the Beckman Institute Molecular Materials Resource Center for assistance and use of their AFM facilities; F. Furuya for help with labelling; and M. Yoder, V. Morozov, D. Stokes, M. Simon and J. Wall for assistance in early attempts to visualize DNA lattices. The research at Caltech has been supported by the National Institute for Mental Health, General Motors' Technology Research Partnerships program, and by the Center for Neuromorphic Systems Engineering as a part of the NSF Engineering Research Center Program. The research at NYU has been supported by the Office of Naval Research, the National Institute of General Medical Sciences, and the NSF.\n\nSupplemental Material - 394539A0.dx.html
Supplemental Material - 394539a0.dna.html
", "abstract": "Molecular self-assembly presents a `bottom-up' approach to the fabrication of objects specified with nanometre precision. DNA\n molecular structures and intermolecular interactions are particularly\n amenable to the design and synthesis of complex molecular objects. We\n report the design and observation of two-dimensional crystalline forms\n of DNA that self-assemble from synthetic DNA double-crossover\n molecules. Intermolecular interactions between the structural units are\n programmed by the design of `sticky ends' that associate according to\n Watson-Crick complementarity, enabling us to create specific periodic\n patterns on the nanometre scale. The patterned crystals have been\n visualized by atomic force microscopy.", "date": "1998-08-06", "date_type": "published", "publication": "Nature", "volume": "394", "number": "6693", "publisher": "Nature Publishing Group", "pagerange": "539-544", "id_number": "CaltechAUTHORS:20110309-104205657", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104205657", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institute of Mental Health (NIMH)" }, { "agency": "General Motors' Technology Research Partnerships" }, { "agency": "Center for Neuromorphic Systems Engineering, Caltech" }, { "agency": "Office of Naval Research (ONR)" }, { "agency": "National Institute of General Medical Sciences" }, { "agency": "NSF" } ] }, "doi": "10.1038/28998", "primary_object": { "basename": "394539A0.dx.html", "url": "https://authors.library.caltech.edu/records/snfgz-51t15/files/394539A0.dx.html" }, "related_objects": [ { "basename": "394539a0.dna.html", "url": "https://authors.library.caltech.edu/records/snfgz-51t15/files/394539a0.dna.html" } ], "resource_type": "article", "pub_year": "1998", "author_list": "Winfree, Erik; Liu, Furong; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jvmmc-dtb97", "eprint_id": 22779, "eprint_status": "archive", "datestamp": "2023-08-22 12:26:03", "lastmod": "2023-10-23 17:11:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Roweis-S", "name": { "family": "Roweis", "given": "Sam" } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" }, { "id": "Burgoyne-R", "name": { "family": "Burgoyne", "given": "Richard" } }, { "id": "Chelyapov-N-V", "name": { "family": "Chelyapov", "given": "Nickolas V." } }, { "id": "Goodman-M-F", "name": { "family": "Goodman", "given": "Myron F." } }, { "id": "Rothemund-P-W-K", "name": { "family": "Rothemund", "given": "Paul W. K." }, "orcid": "0000-0002-1653-3202" }, { "id": "Adleman-L-M", "name": { "family": "Adleman", "given": "Leonard M." } } ] }, "title": "A sticker-based model for DNA computation", "ispublished": "pub", "full_text_status": "public", "keywords": "molecular computation; DNA computation; sticker model", "note": "\u00a9 1998 Mary Ann Leibert, Inc. \n\nReceived for publication November 9, 1997; accepted as revised June 6, 1998. \n\nWe would like to express their appreciation to Professor John Baldeschwieler for his contributions to this\npaper through early discussions of this work. S.R. and E.W. are also grateful to their advisor, Professor John\nHopfield, for his perpetual wisdom and long-term advice. Thanks to Kazuyoshi Harada for some corrections.\nS .R. is supported in part by the Center for Neuromorphic Systems Engineering as a part of the National Science\nFoundation Engineering Research Center Program under grant EEC-9402726 and by the Natural Sciences and\nEngineering Research Council of Canada. E.W. is supported in part by National Institute for Mental Health\n(NIMH) Training Grant no. 5 T32 MH 19138-06; also by General Motors' Technology Research Partnerships\nprogram. L.M.A., N.V.C., and P.W.K.R. are supported in part by grants from the National Science Foundation\n(CCR-9403662) and Sloan Foundation.\n\nPublished - Sticker_Based_Model.pdf
Submitted - stickers_1_.pdf
", "abstract": "We introduce a new model of molecular computation that we call the sticker model. Like many previous proposals it makes use of DNA strands\n as the physical substrate in which information is represented and of\n separation by hybridization as a central mechanism. However, unlike\n previous models, the stickers model has a random access memory that\n requires no strand extension and uses no enzymes; also (at least in\n theory), its materials are reusable. The paper describes computation\n under the stickers model and discusses possible means for physically\n implementing each operation. Finally, we go on to propose a specific\n machine architecture for implementing the stickers model as a\n microprocessor-controlled parallel robotic workstation.\n In the course of this development a number of previous general concerns\n about molecular computation (Smith, 1996; Hartmanis, 1995; Linial ct\n al., 1995) are addressed. First, it is clear that general-purpose\n algorithms can be implemented by DNA-based computers, potentially\n solving a wide class of search problems. Second, we Rnd that there are\n challenging problems, for which only modest volumes of DNA should\n suffice. Third, we demonstrate that the formation and breaking of\n covalent bonds is not intrinsic to DNA-based computation. Fourth, we\n show that a single essential biotechnology, sequence-specific\n separation, suffices for constructing a general-purpose molecular\n computer. Concerns about errors in this separation operation and means\n to reduce them are addressed elsewhere (Karp ct at, 1995; Rowels and\n Winfree, 1999). Despite these encouraging theoretical advances, we\n emphasize that substantial engineering challenges remain at almost all\n stages and that the ultimate success or failure of DNA computing will\n certainly depend on whether these challenges can be met in laboratory\n investigations.", "date": "1998", "date_type": "published", "publication": "Journal of Computational Biology", "volume": "5", "number": "4", "publisher": "Mary Ann Liebert, Inc.", "pagerange": "615-629", "id_number": "CaltechAUTHORS:20110309-104205486", "issn": "1066-5277", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110309-104205486", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "EEC-9402726" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "National Institute of Mental Health (NIMH)", "grant_number": "5 T32 MH 19138-06" }, { "agency": "General Motors' Technology Research Partnerships" }, { "agency": "NSF", "grant_number": "CCR-9403662" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "doi": "10.1089/cmb.1998.5.615", "primary_object": { "basename": "Sticker_Based_Model.pdf", "url": "https://authors.library.caltech.edu/records/jvmmc-dtb97/files/Sticker_Based_Model.pdf" }, "related_objects": [ { "basename": "stickers_1_.pdf", "url": "https://authors.library.caltech.edu/records/jvmmc-dtb97/files/stickers_1_.pdf" } ], "resource_type": "article", "pub_year": "1998", "author_list": "Roweis, Sam; Winfree, Erik; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0z4ss-yr489", "eprint_id": 27383, "eprint_status": "archive", "datestamp": "2023-08-20 06:53:22", "lastmod": "2024-01-13 05:44:06", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "Complexity of Restricted and Unrestricted Models of Molecular Computation", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1996 American Mathematical Society. This work is supported in part by National Institute for Mental Health (NIMH) Training Grant # 5 T32 MH 19138-05; also by General Motors' Technology Research Partnerships program. The author would like to thank Paul W. K. Rothemund, Sam Roweis,\nand Matthew Cook for their stimulating discussion. Thanks especially to Jehoshua Bruck for pointing me to previous literature on branching programs. Thanks to my advisor John Hopfield for his support and encouragement.\n\nPublished - Complexity_Restricted.pdf
Submitted - models_preprint.pdf
", "abstract": "In [9] and [2] a formal model for molecular computing was\nproposed, which makes focused use of affinity purification.\nThe use of PCR was suggested to expand the range of\nfeasible computations, resulting in a second model. In this\nnote, we give a precise characterization of these two models\nin terms of recognized computational complexity classes,\nnamely branching programs (BP) and nondeterministic\nbranching programs (NBP) respectively. This allows us to\ngive upper and lower bounds on the complexity of desired\ncomputations. Examples are given of computable and\nuncomputable problems, given limited time.", "date": "1996", "date_type": "published", "publisher": "American Mathematical Society", "place_of_pub": "Providence, RI", "pagerange": "187-198", "id_number": "CaltechAUTHORS:20111024-134249923", "isbn": "0821805185", "book_title": "DNA based computers", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-134249923", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institute for Mental Health (NIMH) Training Grant", "grant_number": "5 T32 MH 19138-05" }, { "agency": "General Motors Technology Research Partnerships Program" } ] }, "contributors": { "items": [ { "id": "Lipton-R-J", "name": { "family": "Lipton", "given": "Richard J." } }, { "id": "Baum-E-B", "name": { "family": "Baum", "given": "Eric B." } } ] }, "primary_object": { "basename": "Complexity_Restricted.pdf", "url": "https://authors.library.caltech.edu/records/0z4ss-yr489/files/Complexity_Restricted.pdf" }, "related_objects": [ { "basename": "models_preprint.pdf", "url": "https://authors.library.caltech.edu/records/0z4ss-yr489/files/models_preprint.pdf" } ], "resource_type": "book_section", "pub_year": "1996", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0a55p-04j89", "eprint_id": 27382, "eprint_status": "archive", "datestamp": "2023-08-20 06:53:16", "lastmod": "2024-01-13 05:44:04", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-E", "name": { "family": "Winfree", "given": "Erik" }, "orcid": "0000-0002-5899-7523" } ] }, "title": "On the Computational Power of DNA Annealing and Ligation", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 1996 American Mathematical Society.\nThis work is supported in part by National Institute for Mental Health (NIMH) Training Grant # 5 T32 MH 19138-05; also by General Motors' Technology Research Partnerships program.\n\nI would like to thank Paul W. K. Rothemund and Sam Roweis\nfor their stimulating discussion. I am indebted to Ned Seeman for\nmany excellent suggestions, as well as fundamental research on the\nbiochemistry this proposal hopes to exploit; and to Len Adleman\nfor inspiration and great discussions. John Baldeschwieler, Tom\nTheriault, Marc Unger, Sanjoy Mahajan, Carlos Brody, Dave Kewley,\nPam Reinagel, Al Barr, and Stuart Kauffman gave many useful\nsuggestions. Thanks to my advisor John Hopfield for his support and\nencouragement.\n\nPublished - Computational_Power.pdf
Submitted - ligation_preprint.pdf
", "abstract": "In [20] it was shown that the DNA primitives of Separate,\nMerge, and Amplify were not sufficiently powerful to invert\nfunctions defined by circuits in linear time. Dan Boneh et\nal [4] show that the addition of a ligation primitive, Append, provides the missing power. The question becomes, \"How powerful is ligation? Are Separate, Merge, and Amplify\nnecessary at all?\" This paper proposes to informally explore\nthe power of annealing and ligation for DNA computation.\nWe conclude, in fact, that annealing and ligation alone are\ntheoretically capable of universal computation.", "date": "1996", "date_type": "published", "publisher": "American Mathematical Society", "place_of_pub": "Providence, RI", "pagerange": "199-221", "id_number": "CaltechAUTHORS:20111024-133436564", "isbn": "0821805185", "book_title": "DNA Based Computers", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-133436564", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institute for Mental Health (NIMH) Training Grant", "grant_number": "5 T32 MH 19138-05" }, { "agency": "General Motors Technology Research Partnerships Program" } ] }, "contributors": { "items": [ { "id": "Lipton-R-J", "name": { "family": "Lipton", "given": "Richard J." } }, { "id": "Baum-E-B", "name": { "family": "Baum", "given": "Eric B." } } ] }, "primary_object": { "basename": "Computational_Power.pdf", "url": "https://authors.library.caltech.edu/records/0a55p-04j89/files/Computational_Power.pdf" }, "related_objects": [ { "basename": "ligation_preprint.pdf", "url": "https://authors.library.caltech.edu/records/0a55p-04j89/files/ligation_preprint.pdf" } ], "resource_type": "book_section", "pub_year": "1996", "author_list": "Winfree, Erik" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pqvn9-vdy89", "eprint_id": 27385, "eprint_status": "archive", "datestamp": "2023-08-19 17:54:26", "lastmod": "2023-10-24 17:06:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Winfree-A-T", "name": { "family": "Winfree", "given": "A. T." } }, { "id": "Winfree-E", "name": { "family": "Winfree", "given": "E. M." }, "orcid": "0000-0002-5899-7523" }, { "id": "Seifert-H", "name": { "family": "Seifert", "given": "H." } } ] }, "title": "Organizing centers in a cellular excitable medium", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1985 Elsevier Science Publishers.\nReceived 4 January 1985; Available online 9 August 2002.\n\nThis paper was presented at a Symposium on Nonlinear Oscillations in Physiology, Oxford University, 14 September 1984, and printed in the corresponding book of extended abstracts, ed. Derek Linkens.\n\nATW thanks the National Science Foundation for grants CHE 810322 and PCM 8410752. The contents of this paper were first presented at the German Mathematical Society School on Biological Rhythms and Population Dynamics at Bayreuth University in July 1984, courtesy of Volkswagen Foundation. Acknowledgement is made to the Donors of the Petroleum Research Fund administered by the American Chemical Society for partial support of this work.", "abstract": "Excitable media provide much of the subject-matter of physiology, especially of electrophysiology. We simulate excitability in a cubical three-dimensional grid of discrete cells. Topologically distinct organizing centers for self-sustaining rhythmic activity (at period 4) arise from suitable initial conditions. Two are shown: the scroll ring and the linked pair of twisted scroll rings. The first has already been observed in a chemically excitable reagent and possibly in heart muscle; the second, and others of a predicted \"periodic table of organizing centers\", remain to be observed outside computers.", "date": "1985-08", "date_type": "published", "publication": "Physica D", "volume": "17", "number": "1", "publisher": "Elsevier", "pagerange": "109-115", "id_number": "CaltechAUTHORS:20111024-135555583", "issn": "0167-2789", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111024-135555583", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CHE 810322" }, { "agency": "NSF", "grant_number": "PCM 8410752" }, { "agency": "American Chemical Society Petroleum Research Fund" } ] }, "doi": "10.1016/0167-2789(85)90138-1", "resource_type": "article", "pub_year": "1985", "author_list": "Winfree, A. T.; Winfree, E. M.; et el." } ]