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Guiding the folding pathway of DNA origami.

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Title: Guiding the folding pathway of DNA origami.
Authors: Dunn, KE
Dannenberg, F
Ouldridge, TE
Kwiatkowska, M
Turberfield, AJ
Bath, J
Item Type: Journal Article
Abstract: © 2015 Macmillan Publishers Limited.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.
Issue Date: 19-Aug-2015
Date of Acceptance: 16-Jun-2015
URI: http://hdl.handle.net/10044/1/29005
DOI: https://dx.doi.org/10.1038/nature14860
ISSN: 0028-0836
Publisher: Nature Publishing Group
Start Page: 82
End Page: 86
Journal / Book Title: Nature
Volume: 525
Issue: 7567
Copyright Statement: © 2015, Rights Managed by Nature Publishing Group
Keywords: DNA, Single-Stranded
Dimerization
Kinetics
Nanostructures
Nanotechnology
Nucleic Acid Conformation
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences



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