  By exerting mechanical force it is possible to unfold/refold RNA molecules
one at a time. In a small range of forces, an RNA molecule can hop between the
folded and the unfolded state with force-dependent kinetic rates. Here, we
introduce a mesoscopic model to analyze the hopping kinetics of RNA hairpins in
an optical tweezers setup. The model includes different elements of the
experimental setup (beads, handles and RNA sequence) and limitations of the
instrument (time lag of the force-feedback mechanism and finite bandwidth of
data acquisition). We investigated the influence of the instrument on the
measured hopping rates. Results from the model are in good agreement with the
experiments reported in the companion article (1). The comparison between
theory and experiments allowed us to infer the values of the intrinsic
molecular rates of the RNA hairpin alone and to search for the optimal
experimental conditions to do the measurements. We conclude that long handles
and soft laser traps represent the best conditions to extract rate estimates
that are closest to the intrinsic molecular rates. The methodology and
rationale presented here can be applied to other experimental setups and other
molecules.
