Towards a better description and understanding of biomolecular solvation.

We introduce a flexible framework for the correct description of the solvation of biological macromolecules, the dielectric field equation (DFE). The formalism permits the use of any combination of quantum mechanical (QM), molecular mechanical (MM) and continuum electrostatic (CE) based techniques. For the CE region a method that yields the electric field rather than the potential is outlined. The DFE formalism makes clear the need to consider and to calibrate a dielectric boundary region surrounding the simulation system. The details of how to do this are presented for the case of the Ewald summation method; the effects are demonstrated by calculations of the dielectric properties and the spatially resolved Kirkwood G-factor, G(K)(r), of TIP3P water. Computing the dielectric properties of a multi-component system provides a sensitive method to better understand the solvation of biological macromolecules. Towards this goal a rigorous analysis of the dielectric properties of solvated biomolecules based on a decomposition of the frequency-dependent dielectric constant (or susceptibility) of the full system is presented. The meaning of our approach is investigated, and the results of a first application are reported. Using the method of Voronoi polyhedra, the dielectric properties of the first two solvation shells and bulk water are compared by re-analyzing a 12-ns trajectory of a zinc finger peptide in water [Löffler et al. J. Mol. Biol. 270 (1997) 520]. It is found that the first shell behaves considerably different; in addition, there is a non-negligible contribution to the total susceptibility of the system from coupling between the protein and the bulk water phase, i.e. the water molecules not in the immediate vicinity of the solute.