Videos

Folding landscape of RNA from single molecule trajectories

May 20, 2009
Keywords:
  • Cell biology
MSC:
  • 92C37
Abstract
The sequence dependent folding landscapes of nucleic acid hairpins reflect much of the complexity of biomolecular folding. Recently, mechanical folding trajectories, generated using single molecule force clamp experiments by attaching semiflexible polymers to the ends of hairpins have been used to infer their folding landscapes. Using simulations and theory, we study the effect of the dynamics of the attached handles on the RNA free energy profile F(zm), where zm is the molecular extension of the hairpin. Accurate measurements of F(zm) requires stiff polymers with small L/lp, where L is the contour length of the handle, and lp is the persistence length. Paradoxically, reliable estimates of hopping rates can only be made using flexible handles. We show that F(zm) at an external tension fm, the force (f) at which the folded and unfolded states are equally populated, in conjunction with Kramers' theory, can provide accurate estimates of the force-dependent hopping rates in the absence of handles at arbitrary values of f. Our theoretical framework shows that zm is a good reaction coordinate for nucleic acid hairpins under tension.