RNA-Specific Force Field Optimization with CMAP and Reweighting.

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 , named . Extensive validations of tetranucleotides and tetraloops show that 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. can also precisely reproduce the conformation of a duplex and riboswitches. These findings confirm that the newly developed force field can improve the conformer sampling of RNA.