Simple Adjustment of Intra-nucleotide Base-phosphate Interaction in OL3 AMBER Force Field Improves RNA Simulations

Abstract

ABSTRACTMolecular dynamics (MD) simulations represent an established tool to study RNA molecules. Outcome of MD studies depends, however, on the quality of the used force field (ff). Here we suggest a correction for the widely used AMBER OL3ffby adding a simple adjustment of nonbonded parameters. The reparameterization of Lennard-Jones potential for the –H8…O5’– and –H6…O5’– atom pairs addresses an intra-nucleotide steric clash occurring in the type 0 base-phosphate interaction (0BPh). The non-bonded fix (NBfix) modification of 0BPh interactions (the NBfix0BPhmodification) was tuned via reweighting approach and, subsequently, tested using extensive set of standard and enhanced sampling simulations of both unstructured and folded RNA motifs. The modification corrects minor but visible intra-nucleotide clash for theantinucleobase conformation. We observed that structural ensembles of small RNA benchmark motifs simulated with the NBfix0BPhmodification provide better agreement with experiments. No side-effects of the modification were observed in standard simulations of larger structured RNA motifs. We suggest that the combination of OL3 RNAffand NBfix0BPhmodification is a viable option to improve RNA MD simulations.