The role of nucleobase interactions in RNA structure and dynamics

The intricate network of interactions observed in RNA three-dimensional structures is often described in terms of a multitude of geometrical properties, including helical parameters, base pairing/stacking, hydrogen bonding and backbone conformation. We show that a simple molecular representation con-sisting in one oriented bead per nucleotide can ac-count for the fundamental structural properties of RNA. In this framework, canonical Watson-Crick, non-Watson-Crick base-pairing and base-stacking interactions can be unambiguously identified within a well-defined interaction shell. We validate this rep-resentation by performing two independent, com-plementary tests. First, we use it to construct a sequence-independent, knowledge-based scoring function for RNA structural prediction, which com-pares favorably to fully atomistic, state-of-the-art techniques. Second, we define a metric to measure deviation between RNA structures that directly re-ports on the differences in the base–base interaction network. The effectiveness of this metric is tested with respect to the ability to discriminate between structurally and kinetically distant RNA conforma-tions, performing better compared to standard tech-niques. Taken together, our results suggest that this minimalist, nucleobase-centric representation cap-tures the main interactions that are relevant for de-scribing RNA structure and dynamics