Modelling DNA origami self-assembly at the domain level
Journal of Chemical Physics American Institute of Physics 143:16 (2015) 165102
Abstract: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.
Part 1: Special Issue: Quantum Cryptography - celebrating 30 years of BB84, Part 2: Special Issue: DNA Computing and Molecular Programming 2012 Preface
NATURAL COMPUTING 13:4 (2014) 497-498
Programmable energy landscapes for kinetic control of DNA strand displacement.
Nature communications 5 (2014) 5324-5324
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.
Molecular Machinery from DNA: Synthetic Biology from the Bottom up
BIOPHYSICAL JOURNAL 106:2 (2014) 23A-23A
Transport and self-organization across different length scales powered by motor proteins and programmed by DNA
Nature Nanotechnology 9:1 (2014) 44-47