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Influence of protein environment on the electron paramagnetic resonance properties of flavoprotein radicals: a QM/MM study

Ewald Pauwels UGent, Reinout Declerck UGent, Toon Verstraelen UGent, Bart De Sterck UGent, Christopher WM Kay, Veronique Van Speybroeck UGent and Michel Waroquier UGent (2010) JOURNAL OF PHYSICAL CHEMISTRY B. 114(49). p.16655-16665
abstract
The neutral and anionic semiquinone radicals of the flavin adenine dinucleotide (FAD) cofactor noncovalently bound in glucose oxidase from A. niger are examined with the aid of QM/MM molecular modeling methods, enabling complete inclusion of the protein environment. Recently, the electron paramagnetic resonance (EPR) characteristics, the anisotropic g tensor and all the significant hyperfine couplings, of these flavoprotein radicals were determined at high resolution (J. Phys. Chem. B 2008, 112, 3568). A striking difference between the neutral and anionic radical forms was found to be a shift in the g(y) principal value. Within the QM/MM framework, geometry optimization and molecular dynamics simulations are combined with EPR property calculations, employing a recent implementation by some of the authors in the CP2K software package. In this way, spectroscopic characteristics are computed on the fly during the MD simulations of the solvated protein structure, mimicking as best as possible the experimental conditions. The general agreement between calculated and experimental EPR properties is satisfactory and on par with those calculated with other codes (Gaussian 03, ORCA). The protonation state of two histidines (His559 and His516) at the catalytic site of this flavoprotein is found to have a remarkable influence on the isotropic hyperfine coupling of one of the methyl groups on the neutral FAD radical, which is consistent with experimental findings in other flavoproteins (J. Biol. Chem. 2007, 282, 4738). Furthermore, the shift in the g(y) principal values between the neutral and anionic radicals is well reproduced by QM/MM simulations. Incorporation of at least the nearest protein environment of the cofactor radicals proves to be vital for a correct reproduction, indicating that this shift is a global feature of the protein rather than a local one. In addition, QM/MM techniques are used to make a prediction of relative angles between important spectroscopic principal directions, which are not readily determined by conventional EPR experiments. Significantly, the directions of the g(x) and the g(y) components of the g-tensor that lie in the plane of the isoalloxazine moiety are rotated by approximately 590 between the neutral and the anionic radicals.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
G-MATRIX ORIENTATION, MOLECULAR-DYNAMICS, RADIATION-INDUCED RADICALS, FLAVIN ADENINE-DINUCLEOTIDE, SPACE GAUSSIAN PSEUDOPOTENTIALS, DENSITY-FUNCTIONAL THEORY, NUCLEAR DOUBLE-RESONANCE, GLUCOSE-OXIDASE, ASPERGILLUS-NIGER, G-TENSOR
journal title
JOURNAL OF PHYSICAL CHEMISTRY B
J. Phys. Chem. B
volume
114
issue
49
pages
16655 - 16665
Web of Science type
Article
Web of Science id
000284990700075
JCR category
CHEMISTRY, PHYSICAL
JCR impact factor
3.603 (2010)
JCR rank
32/125 (2010)
JCR quartile
2 (2010)
ISSN
1520-6106
DOI
10.1021/jp109763t
project
HPC-UGent: the central High Performance Computing infrastructure of Ghent University
project
HPC-UGent: the central High Performance Computing infrastructure of Ghent University
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1182104
handle
http://hdl.handle.net/1854/LU-1182104
date created
2011-03-04 10:58:31
date last changed
2013-09-17 10:50:06
@article{1182104,
  abstract     = {The neutral and anionic semiquinone radicals of the flavin adenine dinucleotide (FAD) cofactor noncovalently bound in glucose oxidase from A. niger are examined with the aid of QM/MM molecular modeling methods, enabling complete inclusion of the protein environment. Recently, the electron paramagnetic resonance (EPR) characteristics, the anisotropic g tensor and all the significant hyperfine couplings, of these flavoprotein radicals were determined at high resolution (J. Phys. Chem. B 2008, 112, 3568). A striking difference between the neutral and anionic radical forms was found to be a shift in the g(y) principal value. Within the QM/MM framework, geometry optimization and molecular dynamics simulations are combined with EPR property calculations, employing a recent implementation by some of the authors in the CP2K software package. In this way, spectroscopic characteristics are computed on the fly during the MD simulations of the solvated protein structure, mimicking as best as possible the experimental conditions. The general agreement between calculated and experimental EPR properties is satisfactory and on par with those calculated with other codes (Gaussian 03, ORCA). The protonation state of two histidines (His559 and His516) at the catalytic site of this flavoprotein is found to have a remarkable influence on the isotropic hyperfine coupling of one of the methyl groups on the neutral FAD radical, which is consistent with experimental findings in other flavoproteins (J. Biol. Chem. 2007, 282, 4738). Furthermore, the shift in the g(y) principal values between the neutral and anionic radicals is well reproduced by QM/MM simulations. Incorporation of at least the nearest protein environment of the cofactor radicals proves to be vital for a correct reproduction, indicating that this shift is a global feature of the protein rather than a local one. In addition, QM/MM techniques are used to make a prediction of relative angles between important spectroscopic principal directions, which are not readily determined by conventional EPR experiments. Significantly, the directions of the g(x) and the g(y) components of the g-tensor that lie in the plane of the isoalloxazine moiety are rotated by approximately 590 between the neutral and the anionic radicals.},
  author       = {Pauwels, Ewald and Declerck, Reinout and Verstraelen, Toon and De Sterck, Bart and Kay, Christopher WM and Van Speybroeck, Veronique and Waroquier, Michel},
  issn         = {1520-6106},
  journal      = {JOURNAL OF PHYSICAL CHEMISTRY B},
  keyword      = {G-MATRIX ORIENTATION,MOLECULAR-DYNAMICS,RADIATION-INDUCED RADICALS,FLAVIN ADENINE-DINUCLEOTIDE,SPACE GAUSSIAN PSEUDOPOTENTIALS,DENSITY-FUNCTIONAL THEORY,NUCLEAR DOUBLE-RESONANCE,GLUCOSE-OXIDASE,ASPERGILLUS-NIGER,G-TENSOR},
  language     = {eng},
  number       = {49},
  pages        = {16655--16665},
  title        = {Influence of protein environment on the electron paramagnetic resonance properties of flavoprotein radicals: a QM/MM study},
  url          = {http://dx.doi.org/10.1021/jp109763t},
  volume       = {114},
  year         = {2010},
}

Chicago
Pauwels, Ewald, Reinout Declerck, Toon Verstraelen, Bart De Sterck, Christopher WM Kay, Veronique Van Speybroeck, and Michel Waroquier. 2010. “Influence of Protein Environment on the Electron Paramagnetic Resonance Properties of Flavoprotein Radicals: a QM/MM Study.” Journal of Physical Chemistry B 114 (49): 16655–16665.
APA
Pauwels, Ewald, Declerck, R., Verstraelen, T., De Sterck, B., Kay, C. W., Van Speybroeck, V., & Waroquier, M. (2010). Influence of protein environment on the electron paramagnetic resonance properties of flavoprotein radicals: a QM/MM study. JOURNAL OF PHYSICAL CHEMISTRY B, 114(49), 16655–16665.
Vancouver
1.
Pauwels E, Declerck R, Verstraelen T, De Sterck B, Kay CW, Van Speybroeck V, et al. Influence of protein environment on the electron paramagnetic resonance properties of flavoprotein radicals: a QM/MM study. JOURNAL OF PHYSICAL CHEMISTRY B. 2010;114(49):16655–65.
MLA
Pauwels, Ewald, Reinout Declerck, Toon Verstraelen, et al. “Influence of Protein Environment on the Electron Paramagnetic Resonance Properties of Flavoprotein Radicals: a QM/MM Study.” JOURNAL OF PHYSICAL CHEMISTRY B 114.49 (2010): 16655–16665. Print.