DNA hybridization kinetics: zippering, internal displacement and sequence dependence
ArXiv 1303.337 (2013)
Abstract:
While the thermodynamics of DNA hybridization is well understood, much less is known about the kinetics of this classic system. Filling this gap in our understanding has new urgency because DNA nanotechnology often depends critically on binding rates. Here we use a coarse-grained model to explore the hybridization kinetics of DNA oligomers, finding that strand association proceeds through a complex set of intermediate states. Successful binding events start with the formation of a few metastable base-pairing interactions, followed by zippering of the remaining bonds. However, despite reasonably strong interstrand interactions, initial contacts frequently fail to lead to zippering because the typical configurations in which they form differ from typical states of similar enthalpy in the double-stranded equilibrium ensemble. Therefore, if the association process is analyzed on the base-pair (secondary structure) level, it shows non-Markovian behavior. Initial contacts must be stabilized by two or three base pairs before full zippering is likely, resulting in negative effective activation enthalpies. Non-Arrhenius behavior is observed as the number of base pairs in the effective transition state increases with temperature. In addition, we find that alternative pathways involving misbonds can increase association rates. For repetitive sequences, misaligned duplexes frequently rearrange to form fully paired duplexes by two distinct processes which we label `pseudoknot' and `inchworm' internal displacement. We show how the above processes can explain why experimentally observed association rates of GC-rich oligomers are higher than rates of AT-rich equivalents. More generally, we argue that association rates can be modulated by sequence choice.Dynamics of solutes with hydrodynamic interactions: Comparison between Brownian dynamics and stochastic rotation dynamics simulations
PHYSICAL REVIEW E 88:4 (2013) ARTN 043304
Simulating a burnt-bridges DNA motor with a coarse-grained DNA model
Natural Computing Springer Netherlands 13:4 (2012) 535-547
Abstract:
We apply a recently-developed coarse-grained model of DNA, designed to capture the basic physics of nanotechnological DNA systems, to the study of a 'burnt-bridges' DNA motor consisting of a single-stranded cargo that steps processively along a track of single-stranded stators. We demonstrate that the model is able to simulate such a system, and investigate the sensitivity of the stepping process to the spatial separation of stators, finding that an increased distance can suppress successful steps due to the build up of unfavourable tension. The mechanism of suppression suggests that varying the distance between stators could be used as a method for improving signal-to-noise ratios for motors that are required to make a decision at a junction of stators.Coarse-grained simulations of DNA overstretching
ArXiv 1209.5892 (2012)
Abstract:
We use a recently developed coarse-grained model to simulate the overstretching of duplex DNA. Overstretching at 23C occurs at 74 pN in the model, about 6-7 pN higher than the experimental value at equivalent salt conditions. Furthermore, the model reproduces the temperature dependence of the overstretching force well. The mechanism of overstretching is always force-induced melting by unpeeling from the free ends. That we never see S-DNA (overstretched duplex DNA), even though there is clear experimental evidence for this mode of overstretching under certain conditions, suggests that S-DNA is not simply an unstacked but hydrogen-bonded duplex, but instead probably has a more exotic structure.Sequence-dependent thermodynamics of a coarse-grained DNA model
ArXiv 1207.3391 (2012)