Publication:
Molecular Docking as a Promising Predictive Model for Silver Nanoparticle-Mediated Inhibition of Cytochrome P450 Enzymes

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Issued Date

2019

Resource Type

Article

File Type

application/pdf

ISSN

15499596

DOI

10.1021/acs.jcim.9b00572

Other identifier(s)

2-s2.0-85076392241

Rights Holder(s)

Scopus

Bibliographic Citation

Journal of Chemical Information and Modeling. Vol 59, No.12 (2019), p.5126-5134

Suggested Citation

Wasukan N., Kuno M., Maniratanachote R. Molecular Docking as a Promising Predictive Model for Silver Nanoparticle-Mediated Inhibition of Cytochrome P450 Enzymes. Journal of Chemical Information and Modeling. Vol 59, No.12 (2019), p.5126-5134. doi:10.1021/acs.jcim.9b00572 Retrieved from: https://hdl.handle.net/20.500.14740/4991

Title

Molecular Docking as a Promising Predictive Model for Silver Nanoparticle-Mediated Inhibition of Cytochrome P450 Enzymes

Author(s)

Wasukan N.
 Kuno M.
 Maniratanachote R.

Abstract

Cytochrome P450 (CYP) enzymes are responsible for oxidative metabolisms of a large number of xenobiotics. In this study, we investigated interactions of silver nanoparticles (AgNPs) and silver ions (Ag+) with six CYP isoforms, namely, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, within CYP-specific inhibitor-binding pockets by molecular docking and quantum mechanical (QM) calculations. The docking results revealed that the Ag3 cluster, not Ag+, interacted with key amino acids of CYP2C9, CYP2C19, and CYP2D6 within a distance of about 3 Å. Moreover, the QM analysis confirmed that the amino acid residues of these CYP enzymes strongly interacted with the Ag3 cluster, providing more insight into the mechanism of the potential inhibition of CYP enzyme activities. Interestingly, these results are consistent with previous in vitro data indicating that AgNPs inhibited activities of CYP2C and CYP2D in rat liver microsomes. It is suggested that the Ag3 cluster is a minimal unit of AgNPs for in silico modeling. In summary, we demonstrated that molecular docking, together with QM analysis, is a promising tool to predict AgNP-mediated CYP inhibition. These methods are useful for deeper understanding of reaction mechanisms and could be used for other nanomaterials. © 2019 American Chemical Society.

Subject(s)

Amino acids
 Biochemistry
 Metal ions
 Metal nanoparticles
 Molecular modeling
 Quantum theory
 Silver nanoparticles
 Amino acid residues
 Cytochrome p450 enzymes
 Oxidative metabolism
 Potential inhibition
 Predictive modeling
 Rat liver microsomes
 Silver nanoparticles (AgNps)
 Specific inhibitors
 Enzyme inhibition
 Cytochrome P450
 Cytochrome P450 inhibitor
 Isoenzyme
 Metal nanoparticle
 Silver
 Chemistry
 Metabolism
 Molecular docking
 Protein conformation
 Thermodynamics
 Cytochrome P-450 Enzyme Inhibitors
 Cytochrome P-450 Enzyme System
 Isoenzymes
 Metal Nanoparticles
 Molecular Docking Simulation
 Protein Conformation
 Silver
 Thermodynamics

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URI

https://hdl.handle.net/20.500.14740/4991

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Scopus: Year 1983-2021

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