(225j) Quantification of DNA Hybridization Thermodynamics at the Atomistic Level

It is widely accepted that DNA hybridization follows a classic nucleation-zippering mechanism. Sampling the nucleation barrier via conventional MD is notoriously difficult and hence inaccurate. Commonly used advanced sampling approaches are also of limited applicability for high-resolution, all-atom studies of DNA hybridization. Accordingly, several coarse-grained models of DNA have been developed to accurately quantify DNA hybridization thermodynamics. However, for some fundamental questions, such as the influence of base chirality on hybridization, atomistic resolution is required. We describe an order parameter-based advanced-sampling technique to compute the hybridization free energy and melting temperature of DNA oligomers using a recently developed native topology-based order metric. We illustrate the implementation of this technique in a study of chiral perturbations to a DNA oligomer and how effect on hybridization thermodynamics.