Coarse-grained simulations of RNAs allowing for conformational transitions of the sugar pucker

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 3'-endo found in A-form helices. The models neglect the 2'-endo conformation that can be found in B-form helices and other RNA structures and is 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 properly reflect the structural differences between the two conformational states. The parameters of the entire model are optimized against RNA structures and melting temperatures 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.