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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2200935
- author
- Heimdal, Jimmy
LU
; Kaukonen, Markus
LU
; Srnec, Martin
; Rulisek, Lubomir
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- ChemPhysChem
- volume
- 12
- issue
- Online: 29 SEP 2011
- pages
- 3337 - 3347
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000297693200029
- pmid:21960467
- scopus:82955229600
- pmid:21960467
- ISSN
- 1439-7641
- DOI
- 10.1002/cphc.201100339
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- 44ad90af-cba7-48ec-aaa6-1b8a782375d6 (old id 2200935)
- date added to LUP
- 2016-04-01 09:51:00
- date last changed
- 2023-01-01 22:42:43
@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 Inc.}},
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}},
doi = {{10.1002/cphc.201100339}},
volume = {{12}},
year = {{2011}},
}