Study of Protein Hydration Water with the V 4S Structural Index: Focus on Binding Site Description

Abstract

V4S, a new structural indicator for water specially designed to be suitable for hydration andnanoconfined contexts, has been recently introduced and preliminary applied for water in contactwith self-assembled monolayers (SAMs) and graphene-like systems. This index enabled an accurate detection of defective high local density water molecules (called as HDA-like given their structuralresemblance with the high density amorphous ice, HDA). In the present work we shall apply thisnew 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-likemolecular arrangements compared to the bulk. Significantly, we shall show that the concentrationof HDA-like molecules sharply decreases beyond the first hydration layer. Finally, we shall alsoreveal a highly non-uniform spatial distribution of the V4S values for the first hydration shell onthe protein surface, where the higher hydrophobicity inherent to the ligand binding site will beevident from an enrichment in HDA-like molecules as compared to the population exhibited bythe global protein surface.