Internal Loop−Helix Coupling in the Dynamics of the RNA Duplex (GC*C*AGUUCGCUGGC) 2

Molecular dynamics simulations are carried out for a double helical RNA tetradecamer containing a UUCG internal loop. Analysis of four separate trajectories, totaling 12 ns in length, identifies several persistent structural motifs adopted by the internal loop under various conditions. In addition to previously identified water-mediated C:U and G:U hydrogen bonding interactions, two key interpair interactions are identified, namely, cross-step hydrogen bonding between adjacent C:U pairs and cross-strand stacking interactions involving mispaired G, and cross-strand stacking interactions involving the C:U pairs. On the basis of principal component analysis of the full oligomer's motion, these local structures are associated with highly compressed helices, and underwound, elongated helices, respectively.