Equilibrium and nonequilibrium effects in the collapse of a model polypeptide

TL;DR

This study uses molecular simulations to analyze the equilibrium and nonequilibrium dynamics of a model protein's hydrophobic collapse, revealing how collapse pathways and free energy landscapes influence folding behavior.

Contribution

It introduces a method to explicitly calculate the free energy landscape of protein collapse and compares equilibrium and nonequilibrium trajectories to understand folding mechanisms.

Findings

Collapse follows the free energy surface closely

Nonequilibrium effects cause deviations from equilibrium predictions

Diffusion coefficient varies across the free energy landscape

Abstract

We present results of molecular simulations of a model protein whose hydrophobic collapse proceeds as a cascade of downhill transitions between distinct intermediate states. Different intermediates are stabilized by means of appropriate harmonic constraints, allowing explicit calculation of the equilibrium free energy landscape. Nonequilibrium collapse trajectories are simulated independently and compared to diffusion on the calculated free energy surface. We find that collapse generally adheres to this surface, but quantitative agreement is complicated by nonequilibrium effects and by dependence of the diffusion coefficient on position on the surface.