Towards a Polarizable Force Field for RNA based on the Classical Drude Oscillator

Abstract

RNA plays many important roles in the cell, including information transfer, gene regulation, protein synthesis, and catalysis. This diversity in function arises in part from the adoption of complex tertiary structures and interconversion between multiple conformational states in response to bound metabolites or changes in other cellular conditions. Modeling RNA with atomistic resolution using molecular dynamics (MD) simulations requires a high-quality empirical force field that can adequately describe the properties of both canonical and non-canonical structures and is sensitive to environmental conditions. To this end, we are developing a force field for RNA that includes the explicit treatment of electronic polarization using the classical Drude Oscillator model. Optimization is focused on the RNA 2′-hydroxyl group and the phosphodiester backbone targeting 2-D quantum mechanical (QM) potential energy and dipole moment surfaces in combination with condensed phase MD simulations of both canonical and non-canonical RNA structures. Parameter validation involves conducting MD simulations of various RNAs not included in the training set.