Modeling Noncanonical RNA Base Pairs by a Coarse-Grained IsRNA2 Model

Noncanonical base pairs contribute crucially to the three-dimensional architecture of large RNA molecules; however, how to accurately model them remains an open challenge in RNA 3D structure prediction. Here, we report a promising coarse-grained (CG) IsRNA2 model to predict noncanonical base pairs in large RNAs through molecular dynamics simulations. By introducing a five-bead per nucleotide CG representation to reserve the three interacting edges of nucleobases, IsRNA2 accurately models various base-pairing interactions, including both canonical and noncanonical base pairs. A benchmark test indicated that IsRNA2 achieves a comparable performance to the atomic model in de novo modeling of noncanonical RNA structures. In addition, IsRNA2 was able to refine the 3D structure predictions for large RNAs in RNA-puzzle challenges. Finally, the graphics processing unit acceleration was introduced to speed up the sampling efficiency in IsRNA2 for very large RNA molecules. Therefore, the CG IsRNA2 model reported here offers a reliable approach to predict the structures and dynamics of large RNAs.