QM/MM Studies of Structure and Reactivity of Cytochrome P450 Enzymes: Methodology and Selected Applications

Sason Shaik*, Hui Chen, Dandamudi Usharani, Walter Thiel

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

10 Scopus citations

Abstract

The chapter starts with a brief review of quantum mechanical/molecular mechanical (QM/MM) theory covering both the basic methodological aspects and practical issues. Thereafter, selected QM/MM applications are presented that address the structure and reactivity of cytochrome P450 (CYP) enzymes. Topics include the properties of the reactive iron-oxo species (Compound I), the mechanism of its formation from its precursor (Compound 0) in the wild-type enzyme (CYP101) and in some T252X mutants (competition between coupling and uncoupling), the mechanism of the formation of staurosporine from chromopyrrolic acid in CYP StaP, the mechanism of dopamine formation in CYP2D6, and the regulation of the catalytic cycle by the reductase. These case studies highlight the merits of QM/MM investigations for understanding the structure and reactivity of CYP enzymes.

Original languageEnglish
Title of host publicationDrug Metabolism Prediction
PublisherWiley-Blackwell
Pages133-178
Number of pages46
ISBN (Electronic)9783527673261
ISBN (Print)9783527335664
DOIs
StatePublished - 25 Aug 2014

Bibliographical note

Publisher Copyright:
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA. All rights reserved.

Keywords

  • Catalytic cycle
  • Cytochrome P450
  • Electronic structure
  • Enzyme mechanism
  • Quantum mechanical/molecular mechanical method
  • Reactivity

Fingerprint

Dive into the research topics of 'QM/MM Studies of Structure and Reactivity of Cytochrome P450 Enzymes: Methodology and Selected Applications'. Together they form a unique fingerprint.

Cite this