Coarse-grained RNA Simulations with Concerted C2'/C3'-endo Sugar Pucker Transitions

All-atom molecular dynamic simulations are generally restricted by the time scale that can be sampled. To address this issue, various coarse-grained RNA models have been developed. These models often assume the ribose, a 5-membered ring, is fixed in only one conformation, typically the C3’-endo found in A-form helices. The models neglect the C2’-endo conformation found in B-form helices and other RNA structures and are known to influence ion binding and catalytic function in addition to secondary structure propensity. Accordingly, we have developed a coarse-grained RNA force field to include transitions between the two sugar pucker states in order to accurately reproduce RNA structures and thermodynamics. To model the sugar pucker, we train a coarse-grained collective variable that distinguishes between the two states. Using this collective variable, we interpolate between two sets of force field parameters to reflect the structural differences between the two conformational states properly. The parameters of the entire model are optimized against RNA structures utilizing our contrastive divergence algorithm. Our coarse-grained RNA model opens up the opportunities to study complex RNA dynamics especially those coupled to sugar pucker transitions.