Reduction Potentials and Acidity Constants of Mn Superoxide Dismutase Calculated by QM/MM Free-Energy Methods.

Summary, in English

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 pK(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.

• Author: Jimmy Heimdal; Markus Kaukonen; Martin Srnec; Lubomir Rulisek; Ulf Ryde
• Department/s: Computational Chemistry
• Publishing year: 2011
• Language: English
• Pages: 3337-3347
• Publication/Series: ChemPhysChem
• Volume: 12
• Issue: Online: 29 SEP 2011
• Links: http://dx.doi.org/10.1002/cphc.201100339
• Document type: Journal article
• Publisher: John Wiley & Sons Inc.
• Topic: Theoretical Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 1439-7641