Static and dynamic waters in Cu, Zn superoxide dismutase: Molecular dynamics simulation and x-ray experiment

Understanding protein hydration is a crucial, and often underestimated issue, in unraveling protein function. Molecular dynamics (MD) computer simulation can provide a microscopic description of the water behavior. We have applied such a simulative approach to dimeric Photobacterium leiognathi Cu,Zn superoxide dismutase, comparing the water molecule sites determined using 1.0 ns MD simulation with those detected by X-ray crystallography. Of the water molecules detected by the two techniques, 20% fall at common sites. These are evenly distributed over the protein surface and located around crevices, which represent the preferred hydration sites. The water mean residence time, estimated by means of a survival probability function on a given protein hydration shell, is relatively short and increases for low accessibility sites constituted by polar atoms. Water molecules trapped in the dimeric protein intersubunit cavity, as identified in the crystal structure, display a trajectory mainly confined within the cavity. The simulation shows that these water molecules are characterized by relatively short residence times, because they continuously change from one site to another within the cavity, thus hinting at the absence of any relationship between spatial and temporal order for solvent molecules in proximity of protein surface.