Development and applications of Coarse Grained models for RNA

Abstract: In contrast to proteins much less attention has been focused on development of computational models for describing RNA molecules, which are being recognized as playing key roles in many cellular functions. Current atomically detailed force fields are not accurate enough to capture the properties of even simple nucleic acid constructs. In this article, we review our efforts to develop coarse-grained (CG) models that capture the underlying physics for the particular length scale of interest. Two models are discussed. One of them is the Three Interaction Site (TIS) model in which each nucleotide is represented by three beads corresponding to sugar, phosphate, and base. The other is the Self-Organized Polymer (SOP) model in which each nucleotide is represented as a single interaction center. Applications of the TIS model to study the complexity of hairpin formation and the effects of crowding in shifting equilibrium between two conformations in human telomerase pseudoknot are described. The work on crowding illustrates a direct link to the activity of telomerase. We use the SOP model to describe the response of {\it Tetrahymena} ribozyme to force. The simulated unfolding pathways agree well with single molecule pulling experiments. We also review predictions for the unfolding pathways for {\it Azoarcus} ribozyme. The success of the CG applications to describe dynamics in RNA gives hope that more complex processes involving RNA-protein interactions can be tackled using variants of the proposed models.