Residence times of water molecules in the hydration sites of myoglobin

Hydration sites are high-density regions in the three-dimensional time-aver aged solvent structure in molecular dynamics simulations and diffraction ex periments. In a simulation of sperm whale myoglobin, we found 294 such high -density regions. Their positions appear to agree reasonably well with the distributions of waters of hydration found in 38 x-ray and 1 neutron high-r esolution structures of this protein. The hydration sites are characterized by an average occupancy and a combination of residence time parameters des igned to approximate a distribution of residence times. It appears that alt hough the occupancy and residence times of the majority of sites are rather bulk-like, the residence time distribution is shifted toward the longer co mponents, relative to bulk. The sites with particularly long residence time s are located only in the cavities and clefts of the protein. This indicate s that other factors, such as hydrogen bonds and hydrophobicity of underlyi ng protein residues, play a lesser role in determining the residence times of the longest-lived sites.