Is the first hydration shell of lysozyme of higher density than bulk water?

Abstract

Characterization of the physical properties of protein surface hydration water is critical for understanding protein structure and folding. Here, using molecular dynamics simulation, we provide an explanation of recent x-ray and neutron solution scattering data that indicate that the density of water on the surface of lysozyme is significantly higher than that of bulk water. The simulationderived scattering profiles are in excellent agreement with the experiment. In the simulation, the 3-Å-thick first hydration layer is 15% denser than bulk water. About two-thirds of this increase is the result of a geometric contribution that would also be present if the water was unperturbed from the bulk. The remaining third arises from modification of the water structure and dynamics, involving approximately equal contributions from shortening of the average water-water O-O distance and an increase in the coordination number. Variation in the first hydration shell density is shown to be determined by topographical and electrostatic properties of the protein surface. On average, denser water is found in depressions on the surface in which the water dipoles tend to be aligned parallel to each other by the electrostatic field generated by the protein atoms.A characterization of protein hydration is essential for understanding protein structure, folding, and function. This characterization requires elucidating the effects of both the solvent on the protein and the protein on the solvent (1, 2). Concerning the latter effect, detailed information on ordering and dynamical properties of individual, highly perturbed, strongly bound water molecules has been furnished by highresolution x-ray crystallography and NMR spectroscopy (3-10). However, to obtain the data required for a complete thermodynamic description of protein hydration it is necessary to obtain a more global picture in which the solvent is described in terms of probability distributions. Recent work in this direction has used molecular dynamics (MD) simulation (11-13) and novel crystallographic methods (6,7,14) to enable radial distribution functions of water molecules around protein groups in crystals and related quantities to be obtained.It is of particular importance to determine how protein surface water is on average perturbed from the bulk. An intriguing result in this regard was reported by Svergun et al. (15), who combined small-angle scattering (SAS) of x-rays in H 2 O with that of neutrons in H 2 O and D 2 O to show that for lysozyme and other proteins the average density of the first hydration shell (0-3 Å from the surface) is significantly higher than that of bulk water. This finding is consistent with results from MD simulation (16) and the crystallographic work (14). The present article explains the physical origin of this effect. We use MD simulation of lysozyme in explicit water to determine the contributions to the hydration density profile. The MD allows detailed structural properties of the hydration water to be analyzed in the context of the SAS resul...

Proton Momentum Distribution in a Protein Hydration Shell

“…It should be noted that oscillations maxima and minima occur at about p 10 and 20 A ÿ1 , corresponding to 4 and 8 times the quantity 2 =d. Remarkably, the distance d can be then calculated to be 2.5 Å , in good agreement with the average oxygen-oxygen distance of two nearby water molecules adsorbed on the protein surface [29], leading to an hydration shell denser than the bulk water. The dynamical transition driven by water around 200 K [3,4] could be responsible of the reduced distance between hydration water oxygens, thus changing the local structure around protons.…”

Structure, dynamics and reactions of protein hydration water

“…As described in Merzel & Smith (2002b), excellent agreement was found between the SAS profiles calculated from the lysozyme simulation and the experimental results of Svergun et al (1998). The next stage is to decompose the observed density increase.…”

Water–protein interactions from high–resolution protein crystallography

“…The orientational order of water molecules on the protein surface in a MD simulation has also been reported by Merzel & Smith (2002). The effective distance range of the solvent dipole was ca.…”