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.