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

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.

6 pages, 4 figures, Phys. Rev. Lett. (in press)

References in corpus (6)

• 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 Hopping Rates of RNA Hairpins can be Estimated from Accurate Measurement of the Folding Landscapes
• Force dependent fragility in RNA hairpins
• The role of internal chain dynamics on the rupture kinetics of adhesive contacts

Cited by in corpus (8)

• Splitting probabilities as a test of reaction coordinate choice in single-molecule experiments
• Multiple barriers in forced rupture of protein complexes
• Diffusive dynamics of contact formation in disordered polypeptides
• Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty
• RNA under Tension: Folding Landscapes, Kinetic Partitioning Mechanism, and Molecular Tensegrity
• Spectral rate theory for projected two-state kinetics
• The impact of hydrodynamic interactions on protein folding rates depends on temperature
• Extracting folding landscape characteristics of biomolecules using mechanical forces