Folding Kinetics for the Conformational Switch Between Alternative RNA Structures

Abstract

The conformational switching between different conformational states is intrinsic to RNA catalytic and regulatory functions, which oftenly 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. Based on the computational studies, we propose that heat capacity change upon RNA folding may be important for RNA folding kinetics. In addition, we find that noncanonical (tertiary) intraloop interactions in tetraloop hairpins 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.