A Tale of Two Desolvation Potentials: An Investigation of Protein Behavior Under High Hydrostatic Pressure

TL;DR

This study compares two pressure-dependent desolvation potentials in coarse-grained protein models to understand their influence on protein folding behavior under high hydrostatic pressure, validated against experimental data.

Contribution

It provides a systematic comparison of two desolvation potentials and their effects on protein folding under pressure using coarse-grained simulations, highlighting the importance of potential well relationships.

Findings

Protein folding transition depends on potential well minima and pressure.

For volume-reducing proteins, direct contact is less stable at high pressure.

Structure-based models are useful for understanding protein behavior under various conditions.

Abstract

Hydrostatic pressure is a common perturbation to probe the conformations of proteins. There are two common forms of pressure dependent potentials of mean force (PMFs) derived from hydrophobic molecules available for the coarse grained molecular simulations of protein folding and unfolding under hydrostatic pressure. Although both PMF includes a desolvation barrier separating the well of a direct contact and the well of a solvent mediated contact, how these features vary with hydrostatic pressure is still debated. There is a need of a systematic comparison of these two PMFs on a protein. We investigated the two different pressure dependencies on the desolvation potential in a structure based protein model using coarse grained molecular simulations. We compared them to the known behavior a real protein based on experimental evidence. We showed that the protein s folding transition curve on the pressure temperature phase diagram depends on the relationship between the potential well minima and pressure. For protein that reduces the total volume under pressure, it is essential for the PMF to carry the feature that the direct contact well is essential less stable than the water mediated contact well at high pressure. We also comment on the practicality and importance of structure based minimalist models for understanding the phenomenological behavior of a protein under a wide range of phase space.