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Bioinformation. 2012; 8(19): 931–937.
Published online Oct 1, 2012. doi:  10.6026/97320630008931
PMCID: PMC3488835
Computational finding of potential inhibitor for Cytochrome P450 Mono-oxygenases Enzyme of Mycobacterium tuberculosis
Ashwani Sharma,1* Krishna K Subbias,2$ Ophélie Robine,3$ Indu Chaturvedi,4$ Anshul Nigam,1,5$ Nishant Sharma,6 and Prem Prashant Chaudhary7$
1Center of drug discovery research, New Era Proteomics, C-1/31, Yamuna Vihar, New Delhi-110053, India
2Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai – 400076, India
3Mass Spectrometry center, New Era Proteomics, 83 route de Grimard, 33670 Créon, France
4Department of Animal Nutrition, Central Institute of Research on Goats (C.I.R.G.), Makhdoom, Farah, Mathura, UP-281122, India
5Interdisciplinary Programme in Life Science, Pondicherry University,Puducherry-605014 India
6Institute of Human Behaviour & Allied Sciences (IHBAS), Jhilmil, Dilshad Garden Delhi- 110095, India
7Biowits Life Sciences, Computational Biology Section, Yamuna Nagar-135001 ,Haryana, India
$Authors contributed equally
*Ashwani Sharma: ashwansharma/at/gmail.comPhone: 91(0)9711108108
Received September 15, 2012; Accepted September 19, 2012.
Abstract
Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation of organic compounds such as lipids and steroidal hormones therefore remain as potential drug target. Currently available first line anti-tuberculosis drugs have been caused several side effects in the body as well as resistance development by mycobacterium against these drugs, necessitates the considerable need for finding new drugs. Therefore, we propose a structure based computational method to find a new potential inhibitor for cytochrome P450 mono-oxygenases enzyme. Compounds from several ligand databases were docked against the functional sites of 2UUQ (A) through the standard GEMDOCK v2.0 and AUTODOCK4.0 molecular docking tools. Commercially available chemical compound ZINC00004165 (5-[3-(2-nitroimidazol-1-yl) propyl] phenanthridine) has produced top rank with lowest interaction energy of -113.2 (via GEMDOCK) and lowest docking energy of -9.80 kcal/mol (via AUTODOCK) as compared to first line anti TB compounds. Z score and normal distribution analysis verified that the ZINC00004165 compound has more affinity towards 2UUQ in comparison to large number of random population of compounds. ZINC00004165 is also in agreement with the drug likeness properties of Lipinski rule of five without any violation. Therefore, our finding concludes that the commercial compound ZINC00004165 can act as a potential inhibitor against cytochrome P450 mono-oxygenases enzyme of Mycobacterium tuberculosis.
Keywords: Cytochrome P450 mono-oxygenases, Tuberculosis, Ligand database, Docking, Gemdock, Autodock
Les articles de Bioinformation ont été offerts à titre gracieux par
Biomedical Informatics Publishing Group.