Molecular dynamic modeling of CYP51B in complex with azole inhibitors

Journal of Biomolecular Structure & Dynamics
Pan GaoRong-Ling Wu

Abstract

Cytochrome P450 14α-sterol demethylase (CYP51), the key enzyme in sterol biosynthesis pathway, is an important target protein of cholesterol-lowering agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51 family members. In the present study, we have chosen four representative inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb), and voriconazole (Vor), and launched to investigate the binding features of CYP51B-inhibitor and gating characteristics via molecular docking and molecular dynamics (MD) simulations. The results show that the ranking of binding affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the strongest binding affinity, whereas Flu shows the weakest binding affinity. More importantly, based on the calculated binding free energy results, we hypothesize that the nonpolar interactions are the most important contributors, and three key residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor binding. Besides, residue Phe180 may play a molecular switch role in the process of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results show that the major tunnel of Din, Flu, and Teb is located between helix K, FG loop,...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A BellamineM R Waterman
Jan 30, 2002·Trends in Molecular Medicine·Antonella LupettiSteven Kelly
Feb 21, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Leonard B Johnson, Carol A Kauffman
Mar 18, 2004·Molecular and Cellular Endocrinology·Galina I Lepesheva, Michael R Waterman
Sep 13, 2005·Biochemical and Biophysical Research Communications·Michael R Waterman, Galina I Lepesheva
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Jun 24, 2006·BMC Bioinformatics·Martin PetrekJirí Damborský
Sep 12, 2006·Biochimica Et Biophysica Acta·Galina I Lepesheva, Michael R Waterman
Mar 28, 2008·Seminars in Respiratory and Critical Care Medicine·Dimitrios I Zonios, John E Bennett
May 15, 2009·The Journal of Physical Chemistry. B·Kakali Sen, John C Hackett
Oct 14, 2010·Archives of Biochemistry and Biophysics·Kip P ConnerWilliam M Atkins
May 25, 2013·Journal of Chemical Information and Modeling·Jonathan D TyzackRobert C Glen
Nov 12, 2013·Journal of Chemical Information and Modeling·Ying-Lu CuiHong-Xing Zhang
Jun 13, 2015·Journal of Biomolecular Structure & Dynamics·Jing-Rong FanHong-Xing Zhang

❮ Previous
Next ❯

Citations

Mar 10, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Omar Gómez-GarcíaCecilio Álvarez-Toledano
Jan 19, 2019·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Mahdi AbastabarMohammad T Hedayati
May 8, 2019·Journal of Biomolecular Structure & Dynamics·Tayane Honorato Siqueira, Leandro Martínez
Jan 4, 2021·Environmental Pollution·Ana Lopez-AntiaRafael Mateo

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

CAVER
GB
MM
Discovery Studio
AMBER
Gaussian09
SA
CASTp
CDOCKER

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.