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Nat Commun. 2014 Nov 10;5:5324. doi: 10.1038/ncomms6324.

Programmable energy landscapes for kinetic control of DNA strand displacement.

Author information

1
Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
2
Rudolf Peierls Centre for Theoretical Physics, Department of Physics, University of Oxford, 1 Keble Road, Oxford OX1 3NP, UK.

Abstract

DNA is used to construct synthetic systems that sense, actuate, move and compute. The operation of many dynamic DNA devices depends on toehold-mediated strand displacement, by which one DNA strand displaces another from a duplex. Kinetic control of strand displacement is particularly important in autonomous molecular machinery and molecular computation, in which non-equilibrium systems are controlled through rates of competing processes. Here, we introduce a new method based on the creation of mismatched base pairs as kinetic barriers to strand displacement. Reaction rate constants can be tuned across three orders of magnitude by altering the position of such a defect without significantly changing the stabilities of reactants or products. By modelling reaction free-energy landscapes, we explore the mechanistic basis of this control mechanism. We also demonstrate that oxDNA, a coarse-grained model of DNA, is capable of accurately predicting and explaining the impact of mismatches on displacement kinetics.

PMID:
25382214
DOI:
10.1038/ncomms6324
[Indexed for MEDLINE]

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