RNA folding: Conformational statistics, folding kinetics, and ion electrostatics

RNA folding is a remarkably complex problem that involves ion-mediated electrostatic interaction, conformational entropy, base pairing and stacking, and noncanonical interactions. During the past decade, results from a variety of experimental and theoretical studies pointed to (a) the potential ion correlation effect in Mg2+-RNA interactions, (b) the rugged energy landscapes and multistate RNA folding kinetics even for small RNA systems such as hairpins and pseudoknots, (c) the intraloop interactions and sequence-dependent loop free energy, and (d) the strong nonadditivity of chain entropy in RNA pseudoknot and other tertiary folds. Several related issues, which have not been thoroughly resolved, require combined approaches with thermodynamic and kinetic experiments, statistical mechanical modeling, and all-atom computer simulations.