Water Contribution to the Protein Folding and its Relevance in Protein Design and Protein Aggregation

TL;DR

This paper reviews how water influences protein stability and folding, using theoretical models and Monte Carlo simulations to interpret experimental data and explore implications for protein design and disease mitigation.

Contribution

It introduces a theoretical approach combined with simulations to understand water's role in protein behavior, aiding in novel biopolymer design and disease strategies.

Findings

Water significantly affects protein free energy landscapes.

Monte Carlo simulations align with experimental observations.

Insights may inform neurodegenerative disease mitigation.

Abstract

Water plays a fundamental role in protein stability. However, the effect of the properties of water on the behaviour of proteins is only partially understood. Several theories have been proposed to give insight into the mechanisms of cold and pressure denaturation, or the limits of temperature and pressure above which no protein has a stable, functional state, or how unfolding and aggregation are related. Here we review our results based on a theoretical approach that can rationalise the water contribution to protein solutions' free energy. We show, using Monte Carlo simulations, how we can rationalise experimental data with our recent results. We discuss how our findings can help develop new strategies for the design of novel synthetic biopolymers or possible approaches for mitigating neurodegenerative pathologies.