RNA-Specific Force Field Optimization with CMAP and Reweighting.

Abstract

RNA plays a key role in a variety of cell activities. However, it is difficult to capture its structure dynamics by the traditional experimental methods because of the inherent limitations. Molecular dynamics simulation has become a valuable complement to the experimental methods. Previous studies have indicated that the current force fields cannot accurately reproduce the conformations and structural dynamics of RNA. Therefore, an RNA-specific force field was developed to improve the conformation sampling of RNA. The distribution of ζ/α dihedrals of tetranucleotides was optimized by a reweighting method, and the grid-based energy correction map (CMAP) term was first introduced into the Amber RNA force field of ff99bsc0χOL3, named ff99OL3_CMAP1. Extensive validations of tetranucleotides and tetraloops show that ff99OL3_CMAP1 can significantly decrease the population of an incorrect structure, increase the consistency between the simulation results and experimental values for tetranucleotides, and improve the stability of tetraloops. ff99OL3_CMAP1 can also precisely reproduce the conformation of a duplex and riboswitches. These findings confirm that the newly developed force field ff99OL3_CMAP1 can improve the conformer sampling of RNA.