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Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach
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 proliferat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Biomedical Informatics
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498780/ https://www.ncbi.nlm.nih.gov/pubmed/28690380 http://dx.doi.org/10.6026/97320630013144 |
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author | Pandey, Preeti Lynn, Andrew M. Bandyopadhyay, Pradipta |
author_facet | Pandey, Preeti Lynn, Andrew M. Bandyopadhyay, Pradipta |
author_sort | Pandey, Preeti |
collection | PubMed |
description | 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 structurebased 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. |
format | Online Article Text |
id | pubmed-5498780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Biomedical Informatics |
record_format | MEDLINE/PubMed |
spelling | pubmed-54987802017-07-07 Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach Pandey, Preeti Lynn, Andrew M. Bandyopadhyay, Pradipta Bioinformation Hypothesis 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 structurebased 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. Biomedical Informatics 2017-05-31 /pmc/articles/PMC5498780/ /pubmed/28690380 http://dx.doi.org/10.6026/97320630013144 Text en © 2017 Biomedical Informatics http://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Hypothesis Pandey, Preeti Lynn, Andrew M. Bandyopadhyay, Pradipta Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title | Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title_full | Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title_fullStr | Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title_full_unstemmed | Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title_short | Identification of inhibitors against α-Isopropylmalate Synthase of Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach |
title_sort | identification of inhibitors against α-isopropylmalate synthase of mycobacterium tuberculosis using docking-mm/pbsa hybrid approach |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498780/ https://www.ncbi.nlm.nih.gov/pubmed/28690380 http://dx.doi.org/10.6026/97320630013144 |
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