Accurate intraprotein electrostatics derived from first principles: An effective fragment potential method study of the proton affinities of lysine 55 and tyrosine 20 in turkey ovomucoid third domain

A divide-and-conquer method by which an accurate static and induced multipo le representation of the electrostatic potential of a protein can be genera ted using ab initio electronic structure theory is presented. The method is applied to the generation of an effective fragment potential (J. Chem. Phy s. 1996, 105, 1968) for the protein turkey ovomucoid third domain. Dipoles and induced dipoles are necessary for accurate intraprotein electrostatics, as measured by their effects on the gas-phase proton affinities (PAs) of t he amino acid residues lysine 55 (Lys55) and tyrosine 20 (Tyr20). Deprotona tion of Tyr20 is predicted to result in spontaneous proton transfer from Ly s55 to Tyr20, which thus have identical PAs. It is suggested that the exper imentally measured (identical) pK(a)s of Tyr20 and Lys55 might be identical for the same reason.