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Calculation of Reduction Potential and pKa

  1. Jan H. Jensen1,
  2. Hui Li2

Published Online: 15 SEP 2009

DOI: 10.1002/0470862106.ia604

Encyclopedia of Inorganic Chemistry

Encyclopedia of Inorganic Chemistry

How to Cite

Jensen, J. H. and Li, H. 2009. Calculation of Reduction Potential and pKa. Encyclopedia of Inorganic Chemistry. .

Author Information

  1. 1

    University of Copenhagen, Copenhagen, Denmark

  2. 2

    University of Nebraska-Lincoln, Lincoln, NE, USA

Publication History

  1. Published Online: 15 SEP 2009

Abstract

Three methods, quantum mechanical and molecular mechanical polarizable continuum model (QM/MM/PCM), QM/PCM, and empirical, were developed and applied to calculate protein reduction potential (E0) and pKa values. In the QM/MM/PCM calculation of Lys55 pKa of turkey ovomucoid third domain (OMTKY3), the MP2/6-31 + G(2d,p) method was used to describe the QM region consisting of ∼45 atoms; the rest of the protein was modeled either with ab initio-derived electric multipole points or atomic charges from standard force field methods; and the aqueous solvation effect was described with the polarizable continuum model (PCM). The calculated Lys55 pKa values are in good agreement with experiments. QM/PCM methods were used to calculate pKa values of various proteins and the E0 of type-1 Cu centers. For solvent-exposed pKa sites, QM/PCM (MP2/6-31 + G(2d,p) for ∼100 atoms, PCM with dielectric = 78.39 for aqueous solution) methods can often reproduce experimental pKa values. For type-1 Cu E0, because of protein burial, the desolvation effect becomes significant: it was found that Cu-ligand interactions and desolvation can potentially change the E0 by ∼300 and ∼400 mV, respectively, using the CPCM/B3LYP/6-311++G(2df,p) method and model molecules of ∼100 atoms. An empirical method, PROPKA, was developed for protein pKa calculation and analysis, which is able to calculate the pKa values of a protein within ∼1 s.

Keywords:

  • quantum calculation;
  • reduction potential;
  • pKa;
  • OMTKY3;
  • type-1 Cu proteins;
  • PROPKA