Kinetic mechanism of conformational switch between bistable RNA hairpins.

Transitions between the different conformational states play a critical role in many RNA catalytic and regulatory functions. In this study, we use the Kinetic Monte Carlo method to investigate the kinetic mechanism for the conformational switches between bistable RNA hairpins. We find three types of conformational switch pathways for RNA hairpins: refolding after complete unfolding, folding through basepair-exchange pathways and through pseudoknot-assisted pathways, respectively. The result of the competition between the three types of pathways depends mainly on the location of the rate-limiting base stacks (such as the GC base stacks) in the structures. Depending on the structural relationships between the two bistable hairpins, the conformational switch can follow single or multiple dominant pathways. The predicted folding pathways are supported by the activation energy results derived from the Arrhenius plot as well as the NMR spectroscopy data.