Programmable energy landscapes for kinetic control of DNA strand displacement.
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.
Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Robert R F
RR
Machinek
Rudolf Peierls Centre for Theoretical Physics, Department of Physics, University of Oxford, 1 Keble Road, Oxford OX1 3NP, UK.
Thomas E
TE
Ouldridge
Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Natalie E C
NE
Haley
Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Jonathan
J
Bath
Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.
Andrew J
AJ
Turberfield
D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000235:genetics; D012984:Software; D013997:Time Factors
D009841:Oligonucleotides; D004247:DNA