The redox potential of a heme cofactor in cytochrome peroxidase: a polarizable QM/MM study

• Published in: Physical chemistry chemical physics : PCCP 2021-08, Vol.23 (31), p.1656-16515
• Main Authors: Karnaukh, Elizabeth A, Bravaya, Ksenia B
• Format: Article
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/d0cp06632j

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. We present the results of a polarizable QM/MM study of the standard reduction potential of the electron transfer heme in cytochrome c peroxidase of Nitrosomonas europaea and analyze the role of electrostatics in tuning heme redox properties.