Predicting Ion Effects in an RNA Conformational Equilibrium.

We develop a partial charge-based tightly bound ion (PCTBI) model for the ion effects in RNA folding. On the basis of the Monte Carlo tightly bound ion (MCTBI) approach, the model can account for ion fluctuation and correlation effects, and can predict the ion distribution around the RNA. Furthermore, unlike the previous coarse-grained RNA charge models, where negative charges are placed on the phosphates only, the current new model considers the detailed all-atom partial charge distribution on the RNA. Thus, the model not only keeps the advantage of the MCTBI model, but also has the potential to provide important detailed information unattainable by the previous MCTBI models. For example, the model predicts the reduction in ion binding upon protein binding and ion-induced conformational switches. For hepatitis C virus genomic RNA, the model predicts a Mg2+-induced stabilization of a kissing motif for a cis-acting regulatory element in the genomic RNA. Extensive theory-experiment comparisons support the reliability of the theoretical predictions. Therefore, the model may serve as a robust starting point for further development of an accurate method for ion effects in an RNA conformational equilibrium and RNA-cofactor interactions.