Modeling the hydration of proteins at different pH values

The atomic coordinates of proteins, for example, of the enzyme lysozyme as a small model protein, can be used for calculating analytically the exact protein surface in terms of dot surface points and for visualizing both the atoms and the surface points. On the basis of known hydration numbers for the constituent amino acid (AA) residues as suggested by Kuntz and Hopfinger and applying site-specific hydration algorithms implemented in the program HYDCRYST, a modeling of individual water molecules placed at preferred sites on the protein surface can be performed. For this approach, both the bound water molecules and the atoms of the AA residues can be shaped by spheres of appropriate size ("bead modeling"). This also allows the prediction of structural and hydrodynamic molecular parameters by applying any kind of scattering and/or hydrodynamic modeling, in the latter case preferably by the program HYDRO. Use of distinct hydration numbers for different pH ranges allows us to simulate the hydration behavior for changing conditions. The hydration varies in different pH ranges, owing to the variable extent of ionization of the individual AA residues. The transition from neutral to acidic pH values leads to diminished values for the hydration, accompanied by a decrease in the radius of gyration and enhanced values for sedimentation and diffusion coefficients. The comparison of the predicted values for hydration and molecular parameters with observed data is satisfactory within the accuracy of the available experimental data. The prediction of the behavior at alkaline pH values is impeded by insufficient knowledge of the hydration numbers of the AA residues in the basic pH range and the unavailability of experimental reference data.