Compaction and tensile forces determine the accuracy of folding landscape parameters from single molecule pulling experiments

TL;DR

This paper introduces a theoretical framework linking the transition state location in biopolymer folding to measurable forces, enabling better interpretation of single molecule pulling experiments and folding landscape parameters.

Contribution

It develops an analytic theory connecting the transition state to a molecular tensegrity parameter, aiding interpretation of experimental folding data.

Findings

Pfold depends solely on the tensegrity parameter s.

The theory accurately describes folding landscapes of DNA hairpins and leucine zippers.

It provides a method to evaluate if molecular extension is a good reaction coordinate.

Abstract

We establish a framework for assessing whether the transition state location of a biopolymer, which can be inferred from single molecule pulling experiments, corresponds to the ensemble of structures that have equal probability of reaching either the folded or unfolded states (Pfold = 0.5). Using results for the forced-unfolding of a RNA hairpin, an exactly soluble model and an analytic theory, we show that Pfold is solely determined by s, an experimentally measurable molecular tensegrity parameter, which is a ratio of the tensile force and a compaction force that stabilizes the folded state. Applications to folding landscapes of DNA hairpins and leucine zipper with two barriers provide a structural interpretation of single molecule experimental data. Our theory can be used to assess whether molecular extension is a good reaction coordinate using measured free energy profiles.