Probing molecular free energy landscapes by periodic loading

TL;DR

This paper introduces a novel method using periodic loading and Jarzynski's identity to accurately reconstruct biomolecular free energy landscapes from single molecule pulling experiments, especially in unstable barrier regions.

Contribution

The paper presents a new approach combining periodic ramping with Jarzynski's identity to improve free energy profile reconstruction from non-equilibrium data.

Findings

Significantly more accurate free energy profiles than previous methods.

Effective in reconstructing unstable barrier regions.

Requires similar experimental effort as existing techniques.

Abstract

Single molecule pulling experiments provide information about interactions in biomolecules that cannot be obtained by any other method. However, the reconstruction of the molecule's free energy profile from the experimental data is still a challenge, in particular for the unstable barrier regions. We propose a new method for obtaining the full profile by introducing a periodic ramp and using Jarzynski's identity for obtaining equilibrium quantities from non-equilibrium data. Our simulated experiments show that this method delivers significant more accurate data than previous methods, under the constraint of equal experimental effort.