Coarse-Grained Model for Simulation of RNA Three-Dimensional Structures

Abstract

The accurate prediction of an RNA's three-dimensional structure from its "primary structure" will have a tremendous influence on the experimental design and its interpretation and ultimately our understanding of the many functions of RNA. This paper presents a general coarse-grained (CG) potential for modeling RNA 3-D structures. Each nucleotide is represented by five pseudo atoms, two for the backbone (one for the phosphate and another for the sugar) and three for the base to represent base-stacking interactions. The CG potential has been parametrized from statistical analysis of 688 RNA experimental structures. Molecular dynamic simulations of 15 RNA molecules with the length of 12-27 nucleotides have been performed using the CG potential, with performance comparable to that from all-atom simulations. For ~75% of systems tested, simulated annealing led to native-like structures at least once out of multiple repeated runs. Furthermore, with weak distance restraints based on the knowledge of three to five canonical Watson-Crick pairs, all 15 RNAs tested are successfully folded to within 6.5 Å of native structures using the CG potential and simulated annealing. The results reveal that with a limited secondary structure model the current CG potential can reliably predict the 3-D structures for small RNA molecules. We also explored an all-atom force field to construct atomic structures from the CG simulations.