CHARGE SCREENING AND THE DIELECTRIC-CONSTANT OF PROTEINS - INSIGHTS FROM MOLECULAR-DYNAMICS

The dielectric constants of myoglobin, apomyoglobin, the B fragment of staphylococcal protein A, and the immunoglobulin-binding domain of st reptococcal protein G are calculated from 1-2 ns molecular dynamics si mulations in water, using the Frohlich-Kirkwood theory of dielectrics. This dielectric constant is a direct measure of the polarizability of the protein medium and is the appropriate macroscopic quantity to mea sure its relaxation properties in response to a charged perturbation, such as electron transfer, photoexcitation, or ion binding. In each ca se the dielectric constant is low (2-3) in the protein interior, then rises to 11-21 for the whole molecule. The large overall dielectric co nstant is almost entirely due to the charged protein side chains, loca ted at the protein surface, which have significant flexibility. If the se are viewed instead as part of the outer solvent medium, then the re mainder of the protein has a low dielectric constant of 3-6 (depending on the protein), comparable to that of dry protein powders. Similar r esults were already observed for ferro- and ferricytochrome c, and are probably valid for many or most stable globular proteins in solution, leading to a rather comprehensive picture of charge screening and the dielectric constant of proteins. This picture suggests ways, and supp orts some ongoing efforts, to improve current Poisson-Boltzmann models . Indeed, treating a protein as a homogeneous, low dielectric medium i s likely to underestimate the actual dielectric relaxation of the prot ein; this would affect calculations of the self-energy of titrating pr otons, or the reorganization energy of a redox electron.