Dynamics of hydration in hen egg white lysozyme

We investigate the hydration dynamics of a small globular protein, hen egg- white lysozyme. Extensive simulations (two trajectories of 9 ns each) were carried out to identify the time-scales and mechanism of water attachment t o this protein. The location of the surface and integral water molecules in lysozyme was also investigated. Three peculiar temporal scales of the hydr ation dynamics can be discerned: two among these, with sub-nanosecond mean residence time, tau (w), are characteristic of surface hydration water; the slower time-scale (tau (w) similar to 2/3 ns) is associated with buried wa ter molecules in hydrophilic pores and in superficial clefts. The computed tau (w) values in the two independent runs fall in a similar range and are consistent with each other, thus adding extra weight to our result. The tau (w) of surface water obtained from the two independent trajectories is 20 and 24 ps. In both simulations only three water molecules are bound to lyso zyme for the entire length of the trajectories, in agreement with nuclear m agnetic relaxation dispersion estimates. Locations other than those identif ied in the protein crystal are found to be possible for these long-residing water molecules. The dynamics of the hydration water molecules observed in our simulations implies that each water molecule visits a multitude of res idues during the lifetime of its bound with the protein. The number of resi dues seen by a single water molecule increases with the time-scale of its r esidence time and, on average, is equal to one only for the water molecules with shorter residence time. Thus, tau (w) values obtained from inelastic neutron scattering and based on jump-diffusion models are likely not to acc ount for the contribution of water molecules with longer residence time. (C ) 2001 Academic Press.