Effect of temperature, pressure, and cosolvents on structural and dynamic properties of the hydration shell of SNase: a molecular dynamics computer simulation study.

It is now generally agreed that the hydration water and solvational properties play a crucial role in determining the dynamics and hence the functionality of proteins. We present molecular dynamics computer simulation studies on staphylococcal nuclease (SNase) at various temperatures and pressures as well as in different cosolvent solutions containing various concentrations of urea and glycerol. The aim is to provide a molecular level understanding of how different types of cosolvents (chaotropic and kosmotropic) as well as temperature and high hydrostatic pressure modify the structure and dynamics of the hydration water. Taken together, these three intrinsic thermodynamic variables, temperature, pressure, and chemical potential (or activity) of the solvent, are able to influence the stability and function of the protein by protein-solvent dynamic coupling in different ways. A detailed analysis of the structural and dynamical properties of the water and cosolvents at the protein surface (density profile, coordination numbers, hydrogen-bond distribution, average H-bond lifetimes (water-protein and water-water), and average residence time of water in the hydration shell) was carried out, and differences in the structural and dynamical properties of the hydration water in the presence of the different cosolvents and at temperatures between 300 and 400 K and pressures up to 5000 bar are discussed. Furthermore, the results obtained help understand various thermodynamic properties measured for the protein.