Force dependent fragility in RNA hairpins

TL;DR

This paper uses Kramers theory to analyze how RNA hairpins unfold and refold under mechanical force, providing a framework to understand force-induced structural changes and free-energy landscapes.

Contribution

It extends the two-states approximation to include multiple kinetic barriers, enabling detailed analysis of RNA hairpin unfolding under force.

Findings

Identification of two kinetic regimes based on force range

Extension of the two-states approximation validity

Framework for reconstructing free-energy landscapes

Abstract

We apply Kramers theory to investigate the dissociation of multiple bonds under mechanical force and interpret experimental results for the unfolding/refolding force distributions of an RNA hairpin pulled at different loading rates using laser tweezers. We identify two different kinetic regimes depending on the range of forces explored during the unfolding and refolding process. The present approach extends the range of validity of the two-states approximation by providing a theoretical framework to reconstruct free-energy landscapes and identify force-induced structural changes in molecular transition states using single molecule pulling experiments. The method should be applicable to RNA hairpins with multiple kinetic barriers.