Conformational Ensemble of RNA Oligonucleotides from Reweighted Molecular Simulations

Abstract

We determine the conformational ensemble of four RNA tetranucleotides by using available nuclear magnetic spectroscopy data in conjunction with extensive atomistic molecular dynamics simulations. This combination is achieved by applying a reweighting scheme based on the maximum entropy principle. We provide a quantitative estimate for the population of different conformational states by considering different NMR parameters, including distances derived from nuclear Overhauser effect intensities and scalar coupling constants. We show the usefulness of the method as a general tool for studying the conformational dynamics of flexible biomolecules as well as for detecting inaccuracies in molecular dynamics force fields.