Charge Burial Energetics and Protein pKa Shifts Modeled with Nonlocal Electrostatics

Abstract

Continuum electrostatic theory based on the Poisson equation has proven to be a surprisingly effective simple model for understanding protein function, but it has not enjoyed equal success in every application. In particular, calculations of protein pKa shifts have seemed to require substantially different treatment than other calculations. Many groups have found, independently, that pKa calculations match experimental data much better if one adjusts the protein dielectric constant from experimental estimates (which suggest 2 to 5) up to 10 or even higher; this empirically determined parameter has been justified by various physical arguments including implicit protein flexibility.