NDLI: Predicting the binding modes and sites of metabolism of xenobiotics.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mukherjee, Goutam Lal Gupta, Pancham Jayaram, B.
Description	Country affiliation: India Author Affiliation: Mukherjee G ( Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India. bjayaram@chemistry.iitd.res.in.)
Abstract	Metabolism studies are an essential integral part of ADMET profiling of drug candidates to evaluate their safety and efficacy. Cytochrome P-450 (CYP) metabolizes a wide variety of xenobiotics/drugs. The binding modes of these compounds with CYP and their intrinsic reactivities decide the metabolic products. We report here a novel computational protocol, which comprises docking of ligands to heme-containing CYPs and prediction of binding energies through a newly developed scoring function, followed by analyses of the docked structures and molecular orbitals of the ligand molecules, for predicting the sites of metabolism (SOM) of ligands. The calculated binding free energies of 121 heme-containing protein-ligand docked complexes yielded a correlation coefficient of 0.84 against experiment. Molecular orbital analyses of the resultant top three unique poses of the docked complexes provided a success rate of 87% in identifying the experimentally known sites of metabolism of the xenobiotics. The SOM prediction methodology is freely accessible at .
File Format	HTM / HTML
ISSN	1742206X
Issue Number	7
Volume Number	11
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-07-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Cytochrome P-450 Enzyme System Chemistry Xenobiotics Binding Sites Inactivation, Metabolic Molecular Docking Simulation Oxidation-reduction Protein Binding Thermodynamics Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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