Single molecule force spectroscopy

Force
dependent hopping rate of RNA hairpins can be estimated from accurate
measurement of the folding landscapes (PNAS '08)

The
sequence-dependent folding landscapes of nucleic acid hairpins reflect
much of
the complexity of

biomolecular Folding

trajectories,
generated using single molecule force clamp experiments by attaching

semiflexible Using
simulations and theory, we study
the effect of the dynamics of the
attached handles on the handle-free RNA free energy profile

*F*^{o}_{eq}*(**z*_{m}*)*, where

*z*_{m} is the molecular extension of the hairpin.

Accurate measurements of

*F*^{o}_{eq}*(**z*_{m}*)* requires stiff polymers with small

*L/l*_{p},
where

*L* is the contour length of the
handle, and

*l*_{p}
is the persistence length.

Paradoxically,
reliable estimates of the
hopping rates can only be made
using flexible handles.

Nevertheless, we
show that the
equilibrium free energy profile

*F*^{o}_{eq}*(z*_{m})
at an external tension

*f*_{m},
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

*z*_{m}
is a good reaction coordinate for nucleic acid hairpins under tension.