Rational Design of DNA Motors: Fuel Optimization through Single-Molecule Fluorescence

Tomov, Toma E.; Tsukanov, Roman; Liber, Miran; Masoud, Rula; Plavner, Noa; Nir, Eyal

doi:10.1021/ja4048416

Cited by 91 publications

(123 citation statements)

References 46 publications

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“…As noted earlier, experimental results for a DNA walker 54 show an effect analogous to blocking occurring at strand concentrations as low as 50 nM.…”

Section: Discussionsupporting

confidence: 63%

Direct Simulation of the Self-Assembly of a Small DNA Origami

et al. 2016

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By using oxDNA, a coarse-grained nucleotidelevel model of DNA, we are able to directly simulate the self-assembly of a small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, we see attachment of new staple strands occurring in parallel, but with cooperativity evident for the binding of the second domain of a staple if the adjacent junction is already partially formed. For a system with exactly one copy of each staple strand, we observe a complete assembly pathway in an intermediate temperature window; at low temperatures successful assembly is prevented by misbonding while at higher temperature the free-energy barriers to assembly become too large for assembly on our simulation time scales. For high-concentration systems involving a large staple strand excess, we never see complete assembly because there are invariably instances where copies of the same staple both bind to the scaffold, creating a kinetic trap that prevents the complete binding of either staple. This mutual staple blocking could also lead to aggregates of partially formed origamis in real systems, and helps to rationalize certain successful origami design strategies.

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“…As noted earlier, experimental results for a DNA walker 54 show an effect analogous to blocking occurring at strand concentrations as low as 50 nM.…”

Section: Discussionsupporting

confidence: 63%

Direct Simulation of the Self-Assembly of a Small DNA Origami

et al. 2016

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“…11 Even this small leakage drastically limits the scalability of feed-forward, cross-catalytic, and autocatalytic networks, where fuel invasion will unintentionally release the catalyst of the coupled networks. Thermal fluctuations such as fraying have long been suspected as the source of intrinsic leakage, and strategies to suppress it include (1) careful sequence and domain design such as using GC pairs at the fraying locations, 24 (2) use of proper reaction conditions, 47 (3) use of GC-rich sequences or introduction of buffer or clamping domains that are absent from fuel sequences, 36,40 (4) sequestration of domains in hairpin structures, 48 (5) use of extremely pure DNA strands made in bacteria, 26 (6) incorporation of mismatches, 39 and (7) novel domain level redundancy. 49 While each of these approaches has shown some effect, a clear set of design rules have not emerged for consistently and efficiently reducing leakage.…”

Section: Thermal Fluctuations In Dnamentioning

confidence: 99%

Availability: A Metric for Nucleic Acid Strand Displacement Systems

et al. 2016

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DNA strand displacement systems have transformative potential in synthetic biology. While powerful examples have been reported in DNA nanotechnology, such systems are plagued by leakage, which limits network stability, sensitivity, and scalability. An approach to mitigate leakage in DNA nanotechnology, which is applicable to synthetic biology, is to introduce mismatches to complementary fuel sequences at key locations. However, this method overlooks nuances in the secondary structure of the fuel and substrate that impact the leakage reaction kinetics in strand displacement systems. In an effort to quantify the impact of secondary structure on leakage, we introduce the concepts of availability and mutual availability and demonstrate their utility for network analysis. Our approach exposes vulnerable locations on the substrate and quantifies the secondary structure of fuel strands. Using these concepts, a 4-fold reduction in leakage has been achieved. The result is a rational design process that efficiently suppresses leakage and provides new insight into dynamic nucleic acid networks.

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“…6−14 New software also makes designing large nanostructures with tailored properties easier than ever. 15,16 Some of these synthetic structures are static and include crystals, 17−19 polyhedra, 12,20−25 wire-frame designs, 11,26,27 and topological structures such as mobius strips, 28 while others are "active" systems that include walkers, 29,30 gears and hinges, 31 robots, 32,33 and crank-sliders. 34 However, having total control over the structural as well as time-dependent properties of selfassembled DNA nanostructures remains a significant design challenge.…”

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confidence: 99%

Characterizing DNA Star-Tile-Based Nanostructures Using a Coarse-Grained Model

et al. 2016

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We use oxDNA, a coarse-grained model of DNA at the nucleotide level, to simulate large nanoprisms that are composed of multi-arm star tiles, in which the size of bulge loops that have been incorporated into the tile design is used to control the flexibility of the tiles. The oxDNA model predicts equilibrium structures for several different nanoprism designs that are in excellent agreement with the experimental structures as measured by cryoTEM. In particular we reproduce the chiral twisting of the top and bottom faces of the nanoprisms, as the bulge sizes in these structures are varied due to the greater flexibility of larger bulges. We are also able to follow how the properties of the star tiles evolve as the prisms are assembled. Individual star tiles are very flexible, but their structures become increasingly well-defined and rigid as they are incorporated into larger assemblies. oxDNA also finds that the experimentally observed prisms are more stable than their inverted counterparts, but interestingly this preference for the arms of the tiles to bend in a given direction only emerges after they are part of larger assemblies. These results show the potential for oxDNA to provide detailed structural insight as well as to predict the properties of DNA nanostructures and hence to aid rational design in DNA nanotechnology.

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Rational Design of DNA Motors: Fuel Optimization through Single-Molecule Fluorescence

Cited by 91 publications

References 46 publications

Direct Simulation of the Self-Assembly of a Small DNA Origami

Direct Simulation of the Self-Assembly of a Small DNA Origami

Availability: A Metric for Nucleic Acid Strand Displacement Systems

Characterizing DNA Star-Tile-Based Nanostructures Using a Coarse-Grained Model

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