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Title |
Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach
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Authors |
Preeti Pandey, Andrew M. Lynn*, Pradipta Bandyopadhyay*
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Affiliation |
School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, INDIA 110067;
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andrew@jnu.ac.in; praban07@gmail.com
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Article Type |
Hypothesis
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Date |
Received April 18, 2017; Accepted April 21, 2017; Published May 31, 2017
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Abstract |
α-Isopropylmalate Synthase (α-IPMS) encoded by leuA in Mycobacterium tuberculosis (M.tb) is involved in the leucine biosynthesis pathway and is extremely critical for the synthesis of branched-chain amino acids (leucine, isoleucine and valine). α-IPMS activity is required not only for the proliferation of M.tb but is also indispensable for its survival during the latent phase of infection. It is absent in humans and is widely regarded as one of the validated drug targets against Tuberculosis (TB). Despite its essentiality, any study on designing of potential chemical inhibitors against α-IPMS has not been reported so far. In the present study, in silico identification of putative inhibitors against α-IPMS exploring three chemical databases i.e. NCI, DrugBank and ChEMBL is reported through structure based drug design and filtering of ligands based on the pharmacophore feature of the actives. In the absence of experimental results of any inhibitor against α-IPMS, a stringent validation of docking results is done by comparing with molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations by investigating two more proteins for which experimental results are known.
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Keywords |
Inhibitor, α-Isopropylmalate Synthase, Mycobacterium tuberculosis, docking-MM/PBSA hybrid approach
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Citation |
Pandey et al. Bioinformation 13(5): 144-148 (2017)
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
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