Polarizable force field for RNA based on the classical drude oscillator.

Abstract

RNA molecules are highly dynamic and capable of adopting a wide range of complex, folded structures. The factors driving the folding and dynamics of these structures are dependent on a balance of base pairing, hydration, base stacking, ion interactions, and the conformational sampling of the 2'-hydroxyl group in the ribose sugar. The representation of these features is a challenge for empirical force fields used in molecular dynamics simulations. Toward meeting this challenge, the inclusion of explicit electronic polarization is important in accurately modeling RNA structure. In this work, we present a polarizable force field for RNA based on the classical Drude oscillator model, which represents electronic degrees of freedom via negatively charged particles attached to their parent atoms by harmonic springs. Beginning with parametrization against quantum mechanical base stacking interaction energy and conformational energy data, we have extended the Drude-2017 nucleic acid force field to include RNA. The conformational sampling of a range of RNA sequences were used to validate the force field, including canonical A-form RNA duplexes, stem-loops, and complex tertiary folds that bind multiple Mg2+ ions. Overall, the Drude-2017 RNA force field reproduces important properties of these structures, including the conformational sampling of the 2'-hydroxyl and key interactions with Mg2+ ions. © 2018 Wiley Periodicals, Inc.