Effects of lengthscales and attractions on the collapse of hydrophobic polymers in water

TL;DR

This study uses molecular dynamics simulations to explore how lengthscale and attraction strength influence the collapse and folding of hydrophobic polymers in water, revealing temperature-dependent stability and hydration effects.

Contribution

It provides detailed insights into the effects of lengthscale and attractions on hydrophobic polymer folding, incorporating a surface tension model and linking hydration thermodynamics to protein folding.

Findings

Increasing lengthscale stabilizes folded states.

Hydration contribution follows a surface tension model.

Polymer-water interface is soft and weakly dewetted.

Abstract

We present results from extensive molecular dynamics simulations of collapse transitions of hydrophobic polymers in explicit water focused on understanding effects of lengthscale of the hydrophobic surface and of attractive interactions on folding. Hydrophobic polymers display parabolic, protein-like, temperature-dependent free energy of unfolding. Folded states of small attractive polymers are marginally stable at 300 K, and can be unfolded by heating or cooling. Increasing the lengthscale or decreasing the polymer-water attractions stabilizes folded states significantly, the former dominated by the hydration contribution. That hydration contribution can be described by the surface tension model, $\Delta G=\gamma (T)\Delta A$, where the surface tension, $\gamma$, is lengthscale dependent and decreases monotonically with temperature. The resulting variation of the hydration entropy with polymer lengthscale is consistent with theoretical predictions of Huang and Chandler (Proc. Natl. Acad. Sci.,97, 8324-8327, 2000) that explain the blurring of entropy convergence observed in protein folding thermodynamics. Analysis of water structure shows that the polymer-water hydrophobic interface is soft and weakly dewetted, and is characterized by enhanced interfacial density fluctuations. Formation of this interface, which induces polymer folding, is strongly opposed by enthalpy and favored by entropy, similar to the vapor-liquid interface.