A global model of the protein-solvent interface

Abstract

The solvent structure and dynamics around myoglobin is investigated at the microscopic level of detail by computer simulation. We analyze a molecular dynamics trajectory in terms of solvent mobility and probability distribution. Local events, occurring in the protein-solvent interfacial region, which are often masked by other approaches are thus revealed. Specifically, the local solvent mobility is greatly enhanced for certain locations at the protein surface and in its interior. In addition, a strong correlation between the solvent mobility and density emerges on both global and local scales. We propose a simple model where the solvent distribution measured perpendicularly to the protein surface is utilized to reconstruct the simulated network of hydration within 6 A from the protein surface with a relative error of only 17%. The global precision of this solvation model matches results obtained with more complicated models usually used in refinement procedures in x-ray and neutron experiments but with far fewer parameters. The dramatically improved correspondence between observed and calculated x-ray intensities at low resolution relative to other methods both confirms the validity of the approach used in the MD (molecular dynamics) simulations and allows the results of this study to be implemented in solvent studies on real systems.

Structure, dynamics and reactions of protein hydration water

“…Although NMR and crystallography provide detailed information on well-ordered water molecules, to furnish 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 MD simulation (Lounnas et al 1994;Pettitt et al 1998) and novel crystallographic methods (Burling et al 1996) to enable radial distribution functions of water molecules around protein groups in crystals and related quantities to be obtained.…”

Proximal distributions from angular correlations: A measure of the onset of coarse-graining

“…Truncation of n for the Lennard-Jones potential for the very small molecule case considered would lead to large errors for any set of functions chosen, while the Coulomb results are less sensitive as seen in previous work. 3,4,6,7 We note that, because the n = 2, 3 terms oscillate around this result, the conclusion that can be drawn from all of these various results together is that the fundamental conservation of charge rescues the partial sums of the Coulomb potential for the total molecular potential, but as is normal and expected the termby-term convergence of a Coulomb series is not generally so well behaved.…”

“…4 Now, for the left-handed proximal distributions of the macromolecule-water distributions, the m sites are many more than if the right-handed g ij (r, n) functions were used, since n m for water, as in the more common convention. 3,4,[6][7][8] Using the larger number of macromolecular sites to expand the neighbor hierarchy in allows for the fine-grained functionalization of the excess energy per molecule over the m-member hierarchy:…”

“…2 The existence of a series decomposition of the fundamental structural description of a fluid system leads naturally to the question of whether or how the series can be truncated to construct a reduced description of a fluid system which still accurately measures the thermodynamics. To this point, it has been shown [4][5][6][7][8] that the truncation of the neighbor hierarchy of the average solvent distribution around a solute at the nearest neighbor approximation, with suitable renormalization, is a reasonable approximation for the density distribution and thus the electrostatic densities and energies of small biologically interesting molecules. The resulting electrostatic free energies of solvation of the approximate density distributions a) Electronic mail: mpettitt@utmb.edu computed with linear response are within a chemically acceptable error and generally better than continuum solvent approaches.…”

“…We and others 8 have successfully used truncation of one of the series for molecules which are very different in size. Here we use a slightly different set of functions than have previously been studied 3,4,[6][7][8] to measure coarse-graining for large solutes with respect to the smaller solvent molecule interactions.…”