Solvation energetics of proteins and their aggregates analyzed by all-atom molecular dynamics simulations and the energy-representation theory of solvation

Abstract

Solvation is a controlling factor for the structure and function of proteins. This article addresses the effects of solvation from an energetic perspective for the fluctuations and cosolvent-induced changes in protein structures and the equilibrium of aggregate formation for a peptide. A theoretical framework to analyze the solvation effects with an explicit solvent is introduced by adopting the energy-representation theory of solvation, and the connection of the solvation free energy to the protein structure and the aggregation tendency is quantitatively described in combination with all-atom molecular dynamics simulations. The interaction components that govern the solvation effects on the structural variations of proteins are further identified through correlation analysis, and a computational scheme to assess the shift of an aggregation equilibrium due to the addition of a cosolvent is provided.