Thermodynamics of DNA Hybridization from Atomistic Simulations

Abstract Studying the DNA hybridization equilibrium via brute force molecular dynamics (MD) or commonly used advanced sampling approches is notoriously difficult at atomistic lengthscale. However, besides providing a more realistic modeling of this microscopic phenomenon, atomistic resolution is a necessity for some fundamental research questions, such as the ones related to DNA’s chirality. Here, we describe an order parameter-based advanced sampling technique to calculate the free energy surface of hybridization and estimate melting temperature of DNA oligomers at atomistic resolution, using a native topology-based order parameter. We show that the melting temperatures estimated from our atomistic simulations follow an order consistent with the predictions from melting experiments and those from the nearest neighbor model, for a range of DNA sequences of different GC content. Moreover, free energy surfaces and melting temperatures are calculated to be identical for D- and L-enantiomers of Drew-Dickerson dodecamer. biorxiv;2020.08.05.238485v1/UFIG1F1ufig1Graphical TOC Entry