A Computational Investigation of the Origin of Hysteresis in Water Sorption Isotherms of Proteins

Abstract

Understanding the water sorption behavior of proteins is essential to many industrial applications such as the development of cosmetic products and the formulation of long-term preservation techniques of pharmaceutical proteins. Recent advances in computational simulation methods have allowed the systematic computation of water sorption isotherms of proteins. However, the underlying causes of the hysteresis between adsorption and desorption isotherms are not yet clearly understood. Using three model proteins (lysozyme, Trp-cage, and KAP8.1), I investigated the protein-water interactions at a microscopic scale, using metrics such as hydrogen bonding, radial distribution functions, and solvent-accessible surface area. Although these metrics do not explain the hysteresis when averaged over the entire protein surface, noticeable localized differences arise when these metrics are compared on a per-residue basis. These results suggest that hysteresis in water sorption isotherms is associated with local differences in hydration across the protein surfaces. Furthermore, the polar, especially charged, residues primarily contribute to the hysteresis, which are confirmed through mutation studies using Trp-cage.