Base-specific RNA force field improving the dynamics conformation of nucleotide

RNA plays a key role in numerous biological processes. Traditional experimental methods have difficulties capturing the structure and dynamic conformation of RNA. Thus, Molecular dynamic simulations (MDs) has become an essential complementary for RNA experiment. However, state-of-the-art RNA force fields have two major limitations of overestimation base stacking propensity and generation of a high ratio of intercalated conformations. Therefore, a two-step strategy was used to optimize the parameters of ff99bsc0χOL3 (named BSFF1) to improve these limitations, which as well adjusted the unbonded parameters of nucleobase heavy atoms and added ζ/α grid-based energy correction map energy term with reweighting. MD simulations of tetranucleotides indicate that BSFF1 can significantly decrease the ratio of intercalated conformations. Tests of single-strand RNA and kink-turn show that BSFF1 force field can reproduce more accurate conformers than ff99bsc0χOL3 force field. BSFF1 can also stabilize the conformers of duplex and riboswitch. The successful ab initio folding of tetraloop further supports the performance of BSFF1. These findings confirm that the newly developed force field BSFF1 can improve the conformer sampling of RNA.