Nakasako, M. Energy Landscape and Hydration of Proteins. Hydration Structures of Proteins, Springer, 2021, 229-250
At cryogenic temperature, a large number of hydration water molecules around proteins have been identified using X-ray crystal structure analyses, as described in Chap. 2. However, at a glance, it seems that there are no rules governing their distribution. In this chapter, we attempt to classify hydration water molecules with respect to their interaction modes with the protein atoms. Hydration water molecules having direct hydrogen bonds and/or van der Waals contacts are classified as the first-layer class, whereas those without direct interactions are classified as the second-layer class. Hydration water molecules in the first-layer class are the major components in protein hydration, and each water molecule occupies approximately 0.2 nm2 of accessible solvent area on the protein surface. An expected weight ratio of protein versus hydration water molecules range of 0.3–0.4 g-water/g-protein is consistent with the amount necessary for protein function. In addition, the distribution of hydration water molecules found in cryo-crystallography was evaluated by comparing the hydration sites from crystal structures with the solvent density calculated by averaging the trajectory in molecular dynamics simulations. The consistency between the results of crystallography and simulation is indicative of the hydration layer on the surface of the protein in solution.