Diffusion of Solvent around Biomolecular Solutes: A Molecular Dynamics Simulation Study

Abstract

Effects of the macromolecular solute on the translational mobility of surrounding solvent water, and Na+ and Cl- ions are investigated by molecular dynamics (MD) simulation. Using MD trajectories of myoglobin and d(C5T5) . d(G5A5) DNA decamer of high quality and length, we determine the average diffusion coefficients for all solvent species as a function of distance from the closest solute atom. We examine solvent mobility in the directions parallel and perpendicular to the solute surface and in proximity to three different classes of solute atoms (oxygens, nitrogens, and carbons). The nature and the magnitude of the solute effects on water diffusion appear to be very similar for protein and DNA decamer. The overall diffusion rate at the interface is lower than in the bulk. The rate is higher than the average in the direction parallel to the solute surface, and lower in the direction normal to the surface, up to 15 A away from the solute. The rate is also lower in the solvation shells of the macromolecules, producing characteristic depressions in the radial profiles of the diffusion coefficient that can be correlated with peaks in the corresponding radial distribution functions. The magnitude of these depressions is small compared to the overall change in solvent mobility at the interface. Similar features are observed in the radial profiles of the diffusion coefficient of sodium and chlorine ions as well.

An extended dynamical hydration shell around proteins

“…Whereas the existence of hydration layers of over 10 Å has not been reported experimentally, such large layers containing water dynamically distinct from water in the bulk have been found in earlier molecular dynamics simulations (22,23). In addition to the dipole autocorrelation function and terahertz spectra discussed above, a hydration layer corresponding to water dynamics distinct from bulk water can be quantified by the hydrogen bond correlation function, C(t), which yields the probability that a hydrogen bond that exists between two water molecules at a given time, t ϭ 0, is present at a later time, t, regardless whether the bond has been broken between 0 and t. MD simulations of solvated globular * 6-85 at 27°C reveals that the hydrogen bond correlation function for water molecules in 2-Å-thick layers of water up to 10 Å from globular 6-85 * is distinct from the hydrogen bond correlation function computed for bulk water (23), as we show in Fig.…”

Biological water at the protein surface: Dynamical solvation probed directly with femtosecond resolution

“…The nature of this shell ''layer'' has been the focus of numerous studies both theoretically and experimentally (see refs. [5][6][7][8][9][10][11][12]), yet there is no generalized picture of the dynamics at the local molecular level.…”

“…X-ray crystallography, neutron diffraction, and molecular dynamics studies have shown (5)(6)(7)(8)(9)(10) that at protein surfaces, water molecules are site-selective and can be restricted in their motion, even existing in the form of clusters in some cases. For example, neutron diffraction experiments (9) followed by molecular dynamics simulations on carboxymyoglobin (10) revealed that among the 89 water molecules associated with the protein, 4 remain bound during the entire length of the molecular dynamics simulation (50 ps), whereas the rest undergo continuous exchange between bound and free states on a variety of time scales.…”

“…Solvation dynamics in protein environments using dye molecules as extrinsic probes (13)(14) have been studied and show a nonexponential behavior. Molecular dynamics simulations have provided a range of time scales, with distinct difference for the residence time for different sites at the surface (7,8,10). To understand the dynamics at the local molecular scale, several questions need to be addressed: What are the time scales for water relaxation in the immediate vicinity of a protein surface?…”

Transport properties of water at functionalized molecular interfaces

“…By considering water molecules in a finite volume element around biomolecules, numerous attempts have been made to calculate solvent diffusion in the hydration layer of proteins/DNA as a function of distance to the surface. 10,[14][15][16] For viscosity as opposed to diffusion, the stress-stress autocorrelation is often used to calculate the viscosity of the bulk fluid from equilibrium molecular dynamics simulations. 17,18 To access the local viscosity of inhomogeneous fluid, such as fluid confined in nanopores or near imposing walls, nonequilibrium molecular dynamics ͑NEMD͒ has been utilized to simulate fluid under sheer flow.…”