The redox potential of a heme cofactor in Nitrosomonas europaea cytochrome c peroxidase: a polarizable QM/MM study
- 13 May 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Physical Chemistry Chemical Physics
- Vol. 23 (31), 16506-16515
- https://doi.org/10.1039/d0cp06632j
Abstract
Redox reactions are crucial to biological processes that protect organisms against oxidative stress. Metalloenzymes, such as peroxidases which reduce excess reactive oxygen species into water, play a key role in detoxification mechanisms. Here we present the results of a polarizable QM/MM study of the reduction potential of the electron transfer heme in the cytochrome c peroxidase of Nitrosomonas europaea. We have found that environment polarization does not substantially affect the computed value of the redox potential. Particular attention has been given to analyzing the role of electrostatic interactions within the protein environment and the solvent on tuning the redox potential of the heme co-factor. We have found that the electrostatic interactions predominantly explain the fluctuations of the vertical ionization/attachment energies of the heme for the sampled configurations, and that the long range electrostatic interactions (up to 40 Å) contribute substantially to the absolute values of the vertical energy gaps.Keywords
Funding Information
- Alfred P. Sloan Foundation (FG-2020-12877)
- National Institutes of Health (R43GM126804)
This publication has 96 references indexed in Scilit:
- GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkitBioinformatics, 2013
- First-Principle Protocol for Calculating Ionization Energies and Redox Potentials of Solvated Molecules and Ions: Theory and Application to Aqueous Phenol and PhenolateThe Journal of Physical Chemistry B, 2012
- Modulating Heme Redox Potential through Protein-Induced Porphyrin DistortionJournal of the American Chemical Society, 2010
- Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance MechanismsClinical Microbiology Reviews, 2009
- Consistent van der Waals Radii for the Whole Main GroupThe Journal of Physical Chemistry A, 2009
- Candidate Stress Genes ofNitrosomonas europaeafor Monitoring Inhibition of Nitrification by Heavy MetalsApplied and Environmental Microbiology, 2008
- Ligand preference and orientation in b‐ and c‐type heme‐binding proteinsProteins: Structure, Function, and Bioinformatics, 2008
- Canonical sampling through velocity rescalingThe Journal of Chemical Physics, 2007
- All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of ProteinsThe Journal of Physical Chemistry B, 1998
- On optimal and data-based histogramsBiometrika, 1979