Molecular dynamics and advanced sampling simulations of nucleic acids

Abstract

Molecular dynamics (MD) simulations based on a classical force field are increasingly being used to study the structure and dynamics of nucleic acids. Simulation studies are limited by the accuracy of the force field description and by the time scale accessible by current MD approaches. In case of specific conformational transitions, it is often possible to improve the sampling of possible states by adding a biasing or umbrella potential along some coordinate describing the conformational transition. It is also possible to extract the associated free energy change along the reaction coordinate. The development of advanced sampling methods such as the replica-exchange MD (REMD) approach allows significant enhancement of conformational sampling of nucleic acids. Recent applications of umbrella sampling and REMD simulation as well as combinations of both methodologies on nucleic acids will be presented. These approaches have the potential to tackle many open questions in structural biology such as the role of nucleic acid structure during recognition and packing and the function of nucleic acid fine structure and dynamics.