Folding Kinetics for the Conformational Switch between Alternative RNA Structures

Transitions between different conformational states, so-called conformational switching, are intrinsic to RNA catalytic and regulatory functions. Often, conformational switching occurs on time scales of several seconds. In combination with the recent real-time NMR experiments (Wenter et al. Angew. Chem. Int. Ed. 2005, 44, 2600; Wenter et al. ChemBioChem 2006, 7, 417) for the transitions between bistable RNA conformations, we combine the master equation method with the kinetic cluster method to investigate the detailed kinetic mechanism and the factors that govern the folding kinetics. We propose that heat capacity change (∆Cp) upon RNA folding may be important for RNA folding kinetics. In addition, we find that, for tetraloop hairpins, noncanonical (tertiary) intraloop interactions are important to determine the folding kinetics. Furthermore, through theory-experiment comparisons, we find that the different rate models for the fundamental steps (i.e., formation/disruption of a base pair or stack) can cause contrasting results in the theoretical predictions. I