The dynamics of protein hydration water: A quantitative comparison of molecular dynamics simulations and neutron-scattering experiments

We present results from an extensive molecular dynamics simulation study of water hydrating the protein Ribonuclease A, at a series of temperatures in cluster, crystal, and powder environments. The dynamics of protein hydrati on water appear to be very similar in crystal and powder environments at mo derate to high hydration levels. Thus, we contend that experiments performe d on powder samples are appropriate for discussing hydration water dynamics in native protein environments. Our analysis reveals that simulations perf ormed on cluster models consisting of proteins surrounded by a finite water shell with free boundaries are not appropriate for the study of the solven t dynamics. Detailed comparison to available x-ray diffraction and inelasti c neutron-scattering data shows that current generation force fields are ca pable of accurately reproducing the structural and dynamical observables. O n the time scale of tens of picoseconds, at room temperature and high hydra tion, significant water translational diffusion and rotational motion occur . At low hydration, the water molecules are translationally confined but di splay appreciable rotational motion. Below the protein dynamical transition temperature, both translational and rotational motions of the water molecu les are essentially arrested. Taken together, these results suggest that wa ter translational motion is necessary for the structural relaxation that pe rmits anharmonic and diffusive motions in proteins. Furthermore, it appears that the exchange of protein-water hydrogen bonds by water rotational/libr ational motion is not sufficient to permit protein structural relaxation. R ather, the complete exchange of protein-bound water molecules by translatio nal displacement seems to be required.