Recovery of free energy branches in single molecule experiments

TL;DR

This paper introduces a method to accurately determine free energy differences between coexisting states in single molecule experiments using irreversible work measurements and fluctuation relations, validated with optical tweezers.

Contribution

The authors develop a fluctuation relation-based approach to recover free energy branches in dissipative, partially equilibrated systems, demonstrated with single molecule pulling experiments.

Findings

Achieved 0.6 kT accuracy in free energy measurements.

Identified the transition point where native and unfolded states have equal free energy.

Validated the method with optical tweezers experiments.

Abstract

We present a method for determining the free energy of coexisting states from irreversible work measurements. Our approach is based on a fluctuation relation that is valid for dissipative transformations in partially equilibrated systems. To illustrate the validity and usefulness of the approach, we use optical tweezers to determine the free energy branches of the native and unfolded states of a two-state molecule as a function of the pulling control parameter. We determine, within 0.6 kT accuracy, the transition point where the free energies of the native and the unfolded states are equal.