# How the stability of a folded protein depends on interfacial water properties and residue-residue interactions

## TL;DR

This study uses Monte Carlo simulations to explore how interfacial water properties and residue interactions influence protein stability regions in the temperature-pressure plane, aiding biopolymer design.

## Contribution

It demonstrates the critical role of water interface properties in determining protein stability and shows robustness across models and parameters.

## Key findings

- Water properties are essential for stability region shape at low T and high P
- Results are consistent across different protein models and parameters
- Insights can guide the design of synthetic biopolymers

## Abstract

Proteins work only if folded in their native state, but changes in temperature T and pressure P induce their unfolding. Therefore for each protein there is a stability region (SR) in the T-P thermodynamic plane outside which the biomolecule is denaturated. It is known that the extension and shape of the SR depend on i) the specific protein residue-residue interactions in the native state of the amino acids sequence and ii) the water properties at the hydration interface. Here we analyze by Monte Carlo simulations of different coarse-grained protein models in explicit water how changes in i) and ii) affect the SR. We show that the solvent properties ii) are essential to rationalize the SR shape at low T and high P and that our finding are robust with respect to parameter changes and with respect to different protein models. These results can help in developing new strategies for the design of novel synthetic biopolymers.