Force Dependent Hopping Rates of RNA Hairpins can be Estimated from Accurate Measurement of the Folding Landscapes

Abstract

The sequence-dependent folding landscapes of nucleic acid hairpins reflect much of the complexity of biomolecular folding. 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 handle-free RNA free energy profile $F_{eq}^o(z_m)$, where $z_m$ is the molecular extension of the hairpin. Accurate measurements of $F_{eq}^o(z_m)$ 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 $F_{eq}^o(z_m)$ 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.

26 pages, 9 figures

References in corpus (4)

• Forced-unfolding and force-quench refolding of RNA hairpins
• Mechanical unfolding of RNA: From hairpins to structures with internal multiloops
• Measuring the energy landscape roughness and the transition state location of biomolecules using single molecule mechanical unfolding experiments
• Force dependent fragility in RNA hairpins

Cited by in corpus (9)

• How accurate are polymer models in the analysis of Forster resonance energy transfer experiments on proteins?
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• Improving signal-to-noise resolution in single molecule experiments using molecular constructs with short handles
• Dynamic force spectroscopy of DNA hairpins. I. Force kinetics and free energy landscapes
• Measurement of work in single-molecule experiments
• Deconvolution of dynamic mechanical networks
• RNA under Tension: Folding Landscapes, Kinetic Partitioning Mechanism, and Molecular Tensegrity
• Equilibrium properties and force-driven unfolding pathways of RNA molecules
• Theoretical Perspectives on Protein Folding