Study of Protein Hydration Water with the V4S Structural Index: Focus on Binding Site Description.

Abstract

V4S, a new structural indicator for water specially designed to be suitable for hydration and nanoconfined contexts, has been recently introduced and preliminarily applied for water in contact with self-assembled monolayers and graphene-like systems. This index enabled an accurate detection of defective high local density water molecules (called HDA-like given their structural resemblance with the high-density amorphous ice, HDA). In the present work, we shall apply this new metric to characterize protein hydration water with particular interest in protein binding sites. As a first result, we shall find that protein hydration water has a higher concentration of HDA-like molecular arrangements compared to the bulk. Significantly, we shall show that the concentration of HDA-like molecules sharply decreases beyond the first hydration layer. Finally, we shall also reveal a highly nonuniform spatial distribution of the V4S values for the first hydration shell on the protein surface, where the higher hydrophobicity inherent to the ligand binding site will be evident from an enrichment in HDA-like molecules as compared to the population exhibited by the global protein surface.