Protein vicinity water dynamics investigated by molecular dynamics

Abstract This study investigates the dynamics of water molecules within the hydration shells of proteins using molecular dynamics (MD) simulations. Eight proteins—lysozyme (LYZ), β-lactoglobulin, bovine serum albumin (BSA), Pseudomonas aeruginosa (OprF and OprD), myoglobin, bovine hemoglobin, and human pepsin—were examined. Hydration-water residence dynamics were characterized using the residence autocorrelation function, Cr(t), and the corresponding characteristic relaxation time. Water molecules associated with most protein surfaces exhibited longer residence times than bulk water, although the extent of retardation varied among proteins. The resulting relaxation times were comparable to those reported for intermediate water in PMEA membranes, suggesting similarities in their dynamical behavior. Analysis of surface-exposed amino acid residues indicated that hydration-water dynamics are influenced by the hydrophilic/hydrophobic character of the protein surface. In contrast, the density of protein–water hydrogen bonds alone did not correlate directly with the relaxation time. The effect of protein protonation state on hydration-water dynamics was further investigated for LYZ and BSA at pH 3.0, 7.0, and 11.0. These results provide molecular-level insight into the factors governing protein hydration-water dynamics.