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

Heimdal, Jimmy LU ; Kaukonen, Markus LU ; Srnec, Martin; Rulisek, Lubomir LU and Ryde, Ulf LU (2011) In ChemPhysChem 12(Online: 29 SEP 2011). p.3337-3347
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ChemPhysChem
volume
12
issue
Online: 29 SEP 2011
pages
3337 - 3347
publisher
John Wiley & Sons
external identifiers
  • wos:000297693200029
  • pmid:21960467
  • scopus:82955229600
ISSN
1439-7641
DOI
10.1002/cphc.201100339
language
English
LU publication?
yes
id
44ad90af-cba7-48ec-aaa6-1b8a782375d6 (old id 2200935)
date added to LUP
2011-11-09 11:34:40
date last changed
2017-09-24 03:01:17
@article{44ad90af-cba7-48ec-aaa6-1b8a782375d6,
  abstract     = {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       = {Heimdal, Jimmy and Kaukonen, Markus and Srnec, Martin and Rulisek, Lubomir and Ryde, Ulf},
  issn         = {1439-7641},
  language     = {eng},
  number       = {Online: 29 SEP 2011},
  pages        = {3337--3347},
  publisher    = {John Wiley & Sons},
  series       = {ChemPhysChem},
  title        = {Reduction Potentials and Acidity Constants of Mn Superoxide Dismutase Calculated by QM/MM Free-Energy Methods.},
  url          = {http://dx.doi.org/10.1002/cphc.201100339},
  volume       = {12},
  year         = {2011},
}