Folding landscape of RNA from single molecule trajectories
Presenter
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.