Human Serum Albumin: 3D Insight on Protein Hydration.

Human serum albumin (HSA) is one of the main proteins in human blood plasma and serves as a molecular "taxi" transporting various compounds, including organic compounds, drugs, metal ions, etc., through the circulatory system throughout the human body. As with any other proteins, HSA hydration plays an important role in maintaining its structure and functioning as well as influencing its ability to bind to ligands. This contribution presents, for the first time, a generalized picture of hydration of this biomacromolecule obtained within the framework of the 3D-RISM (three-dimensional Reference Interaction Site Model) theory of solvation. Based on 3D isodensity maps and structural parameters (hydration numbers, hydration layer thickness, fraction of hydrogen bonds, SASA, etc.), the most probable model of HSA hydration structure was reconstructed. With the description of HSA hydration, two important issues were also addressed in detail. The first is the correct determination of the hydration layer thickness, a common problem in protein science. The second is the possible state and behavior of hydration water in HSA-ligand binding. The presented results provide a deeper understanding of the relationship between solvent and HSA, which brings new knowledge to the understanding of protein hydration.