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Calculation of amino acid pK a S in a protein from a continuum electrostatic model: Method and sensitivity analysis
Author(s) -
Beroza P.,
Fredkin D. R.
Publication year - 1996
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/(sici)1096-987x(19960730)17:10<1229::aid-jcc4>3.0.co;2-q
Subject(s) - acid dissociation constant , solvent models , chemistry , computational chemistry , poisson–boltzmann equation , solvation , molecule , ion , aqueous solution , organic chemistry
We used continuum electrostatic theory to calculate pK a s of amino acids in protein. A Green's function formalism, based on a finite‐difference solution to the Poisson–Boltzmann equation for a 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. Improvements over previous methods include the ability to focus the finite difference grid to arbitrarily small grid spacing, an analytical representation of the molecular surface, and a novel procedure to calculate the reaction field potential. Using this method, we performed a sensitivity analysis of calculated pK a s in the photosynthetic reaction center. Calculated pK a s are most sensitive for residues thatare not well‐exposed to solvent. Variations in the parameters of the continuum electrostatic model cause pK a shifts that are larger than the accuracy of the numerical method, but probably not large enough to account for some of the discrepancies between calculated and experimentally measured pK a sthat have been reported for the reaction center. © 1996 by John Wiley & Sons,Inc.