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  • 1
    Publication Date: 2015-08-20
    Description: DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development and become a reliable manufacturing technology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dunn, Katherine E -- Dannenberg, Frits -- Ouldridge, Thomas E -- Kwiatkowska, Marta -- Turberfield, Andrew J -- Bath, Jonathan -- England -- Nature. 2015 Sep 3;525(7567):82-6. doi: 10.1038/nature14860. Epub 2015 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Oxford, Department of Physics, Clarendon Laboratory, Parks Road, Oxford OX1 3PU, UK. ; University of Oxford, Department of Computer Science, Wolfson Building, Parks Road, Oxford OX1 3QD, UK. ; University of Oxford, Department of Physics, Rudolf Peierls Centre for Theoretical Physics, 1 Keble Road, Oxford OX1 3NP, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26287459" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Single-Stranded/*chemistry/genetics ; Dimerization ; Kinetics ; Nanostructures/*chemistry ; Nanotechnology ; *Nucleic Acid Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2005-12-13
    Description: Practical components for three-dimensional molecular nanofabrication must be simple to produce, stereopure, rigid, and adaptable. We report a family of DNA tetrahedra, less than 10 nanometers on a side, that can self-assemble in seconds with near-quantitative yield of one diastereomer. They can be connected by programmable DNA linkers. Their triangulated architecture confers structural stability; by compressing a DNA tetrahedron with an atomic force microscope, we have measured the axial compressibility of DNA and observed the buckling of the double helix under high loads.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodman, R P -- Schaap, I A T -- Tardin, C F -- Erben, C M -- Berry, R M -- Schmidt, C F -- Turberfield, A J -- New York, N.Y. -- Science. 2005 Dec 9;310(5754):1661-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16339440" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Chemistry, Physical ; DNA/*chemistry ; Dimerization ; Elasticity ; Microscopy, Atomic Force ; Models, Molecular ; Molecular Structure ; *Nanostructures ; *Nanotechnology ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry ; Physicochemical Phenomena ; Stereoisomerism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2017-09-17
    Description: Accounts of Chemical Research DOI: 10.1021/acs.accounts.7b00280
    Print ISSN: 0001-4842
    Electronic ISSN: 1520-4898
    Topics: Chemistry and Pharmacology
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  • 4
    Publication Date: 2007-11-17
    Description: Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, David Yu -- Turberfield, Andrew J -- Yurke, Bernard -- Winfree, Erik -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1121-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computation and Neural Systems, California Institute of Technology, MC 136-93, 1200 East California Boulevard, Pasadena, CA91125, USA. dzhang@dna.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalysis ; Chemical Engineering ; *Computers, Molecular ; DNA/*chemistry ; Entropy ; Equipment Design ; Feedback, Physiological ; Mice ; Nanotechnology ; Nucleic Acid Hybridization ; Rabbits
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-10-29
    Description: We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling, and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.
    Electronic ISSN: 1931-9223
    Topics: Chemistry and Pharmacology , Physics
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  • 6
    Publication Date: 2015-10-29
    Description: We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling, and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.
    Print ISSN: 0021-9606
    Electronic ISSN: 1089-7690
    Topics: Chemistry and Pharmacology , Physics
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  • 7
    Publication Date: 2014-11-12
    Description: Article The operation of DNA-based molecular devices often relies on toehold-mediated strand displacement. Here, the authors show how mismatches in base pairing can be used for the kinetic control of strand displacement, tuning the rate constant over three orders of magnitude. Nature Communications doi: 10.1038/ncomms6324 Authors: Robert R. F. Machinek, Thomas E. Ouldridge, Natalie E. C. Haley, Jonathan Bath, Andrew J. Turberfield
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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