HiRE-RNA: A High Resolution Coarse-Grained Energy Model for RNA

Abstract

Although RNAs play many cellular functions, the gap between their sequences and 3D structures is increasing and our knowledge of RNA thermodynamics and long time scale dynamics is still limited at an atomic level of detail. In principle, all-atom molecular dynamics (MD) and replica exchange molecular dynamics (REMD) simulations can investigate these issues, but with current computer facilities, these simulations in explicit solvent have been limited to small RNAs and to short times. To move to larger systems, we can resort to coarse-graining. In this study, we present HiRE-RNA, a generic high resolution coarse-grained model for RNA, and report MD and REMD simulations on two RNAs of 22 and 36 nucleotides. Starting from unfolded structures, the 22-mer folds within 1.8 A rmsd from the NMR structure, while the 36-mer folds within 4.6 A rmsd. Current results suggest that further optimization of the HiRE-RNA force field should open the door to a relevant model for studying large RNAs, such as riboswitches, and for predicting 3D structures from secondary structure information.