The structural plasticity of RNA and the many complex folds RNA sequences can adopt require robust physical models for understanding the driving forces for RNA structure, folding, and function, and the rational modulation of those properties. Given the polyanionic nature of RNA and the requirement of many RNA sequences to interact with divalent cations to fold, accurate representation of electrostatics in an empirical force field model for RNA is critical. Here, we present a polarizable force field for RNA using the classical Drude oscillator model, in which electronic degrees of freedom are represented by negatively charged particles attached to their parent atoms via harmonic springs. The force field is parametrized by targeting quantum mechanical interaction energy data (base stacking and interactions with water and ions) as well as conformational energy profiles of model compounds, with particular emphasis on the properties of the 2’-hydroxyl group that dictates, in part, RNA conformational heterogeneity. Validation of the force field involved simulating canonical, double-stranded RNA and a variety of non-canonical structures ranging from secondary structures such as stem-loops to tertiary folds that bind multiple Mg<sup>2+</sup> ions. Comparisons are made to available crystal survey and NMR data. The Drude polarizable model allows for dipole response to variations in hydration and mobile ions that influence the electric field around RNA, effects that cannot be observed using traditional fixed-charge force fields. As such, the development of this polarizable RNA force field represents a significant step forward in simulation technology for modeling and understanding complex nucleic acid systems.

Empirical polarizable force field for RNA based on the classical Drude oscillator model

254th National Meeting (2017)

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