CALCULATION OF AMINO-ACID PK(A)S IN A PROTEIN FROM A CONTINUUM ELECTROSTATIC MODEL - METHOD AND SENSITIVITY ANALYSIS

We used continuum electrostatic theory to calculate pK(a)s of amino ac ids in protein. A Green's function formalism, based on a finite-differ ence solution to the Poisson-Boltzmann equation fora unit point charge , yields electrostatic potentials that allow calculation of amino acid pK(a)s to an estimated accuracy of tenths of a pK(a) unit. Improvemen ts over previous methods include the ability to focus the finite diffe rence grid to arbitrarily small grid spacing, an analytical representa tion of the molecular surface, and a novel procedure to calculate the reaction field potential. Using this method, we performed a sensitivit y analysis of calculated pK(a)s in the photosynthetic reaction center. Calculated pK(a)s are most sensitive for residues that are not well-e xposed to solvent. Variations in the parameters of the continuum elect rostatic model cause pK(a) shifts that are larger than the accuracy of the numerical method, but probably not large enough to account for so me of the discrepancies between calculated and experimentally measured pK(a)s that have been reported for the reaction center. (C) 1996 by J ohn Wiley & Sons, Inc.