A possible mechanism for cold denaturation of proteins at high pressure

TL;DR

This study investigates how high pressure influences protein cold denaturation, revealing that water density fluctuations and loss of low-density water structures drive the process, aligning with experimental data.

Contribution

It introduces a multicanonical Monte Carlo simulation approach to model protein denaturation under high pressure, emphasizing water's role in the mechanism.

Findings

Cold denaturation occurs above 2 kbar pressure.

Loss of low-density water structure triggers denaturation.

Simulation results agree with experimental data.

Abstract

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.