Transition Path Times for Nucleic Acid Folding Determined from Energy-Landscape Analysis of Single-Molecule Trajectories

The duration of structural transitions in biopolymers is only a fraction of the time spent searching diffusively over the configurational energy landscape. We found the transition time, tau(TP), and the diffusion constant, D, for DNA and RNA folding using energy landscapes obtained from single-molecule trajectories under tension in optical traps. DNA hairpins, RNA pseudoknots, and a riboswitch all had tau(TP) similar to 10 mu s and D similar to 10(-13-14) m(2)/s, despite widely differing unfolding rates. These results show how energy-landscape analysis can be harnessed to characterize brief but critical events during folding reactions.