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Reduction Potentials and Acidity Constants of Mn Superoxide Dismutase Calculated by QM/MM Free‐Energy Methods
Author(s) -
Heimdal Jimmy,
Kaukonen Markus,
Srnec Martin,
Rulíšek Lubomír,
Ryde Ulf
Publication year - 2011
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201100339
Subject(s) - solvation , chemistry , qm/mm , implicit solvation , solvent models , thermodynamics , computational chemistry , density functional theory , molecular dynamics , solvent , physics , organic chemistry
We used two theoretical methods to estimate reduction potentials and acidity constants in Mn superoxide dismutase (MnSOD), namely combined quantum mechanical and molecular mechanics (QM/MM) thermodynamic cycle perturbation (QTCP) and the QM/MM‐PBSA approach. In the latter, QM/MM energies are combined with continuum solvation energies calculated by solving the Poisson–Boltzmann equation (PB) or by the generalised Born approach (GB) and non‐polar solvation energies calculated from the solvent‐exposed surface area. We show that using the QTCP method, we can obtain accurate and precise estimates of the proton‐coupled reduction potential for MnSOD, 0.30±0.01 V, which compares favourably with experimental estimates of 0.26–0.40 V. However, the calculated potentials depend strongly on the DFT functional used: The B3LYP functional gives 0.6 V more positive potentials than the PBE functional. The QM/MM‐PBSA approach leads to somewhat too high reduction potentials for the coupled reaction and the results depend on the solvation model used. For reactions involving a change in the net charge of the metal site, the corresponding results differ by up to 1.3 V or 24 p K a units, rendering the QM/MM‐PBSA method useless to determine absolute potentials. However, it may still be useful to estimate relative shifts, although the QTCP method is expected to be more accurate.