Residence Times of Water Molecules in the Hydration Sites of Myoglobin

Abstract

Hydration sites are high-density regions in the three-dimensional time-averaged solvent structure in molecular dynamics simulations and diffraction experiments. 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-resolution structures of this protein. The hydration sites are characterized by an average occupancy and a combination of residence time parameters designed to approximate a distribution of residence times. It appears that although the occupancy and residence times of the majority of sites are rather bulk-like, the residence time distribution is shifted toward the longer components, relative to bulk. The sites with particularly long residence times are located only in the cavities and clefts of the protein. This indicates that other factors, such as hydrogen bonds and hydrophobicity of underlying protein residues, play a lesser role in determining the residence times of the longest-lived sites.

The Multiple Roles of Waters in Protein Solvation

“…Water molecules showing long residence times on the surface of the protein are uncommon for any protein fold, and water molecules continuously bound to a single residue are extremely rare (see Figure 5), as was in fact anticipated from static measures (see above). In summary, the concept of structural waters as defined from X-Ray crystallography does not fit well with the dynamic picture of solvation derived from our simulations where, as discussed by others (for example 7,9,[17][18][19] ), fast exchange of protein-interacting water is a universal trend.…”

Protein hydration dynamics in solution: a critical survey

“…Water molecules located in surface depressions experience geometric constraints that prevent the cooperative motions responsible for the fast rotational and translational dynamics in bulk water (see § 3). This MRD-derived picture of protein hydration dynamics is supported by several recent simulation studies that have confirmed the importance of surface topography and have failed to establish a correlation between water residence times and the chemical structure, charge or polarity of the contacting groups (Kovacs et al 1997;Luise et al 2000;Makarov et al 2000;Henchman & McCammon 2002).…”

“…If the hydration layer consisted of 'free' and 'bound' water molecules, as postulated, then one would expect bimodal distributions of residence times and rotational correlation times for hydration water. However, all simulations show that these distributions are unimodal (Abseher et al 1996;Luise et al 2000;Makarov et al 2000;Marchi et al 2002;Henchman & McCammon 2002). Also, from a structuralenergetic point of view, the notion of 'free' and 'bound' water molecules in the hydration layer is objectionable.…”

Collapse of the hydration shell of a protein prior to thermal unfolding

“…They showed the existence of a hydration shell whose average density is around 10% larger than that of the bulk water. Molecular dynamics simulation studies also suggested that the variation in the first hydration shell density is subject to the electrostatic properties of the protein surface and local surface topography (Makarov et al, 1998(Makarov et al, , 2000Dastidar & Mukhopadhyay, 2003). However, the properties of the hydrated water shells are still the subject of many experimental and theoretical investigations.…”