Virtual Screening of potential drug-like inhibitors against Lysine/DAP pathway of Mycobacterium tuberculosis.

BMC Bioinformatics
Aarti GargGajendra P S Raghava

Abstract

An explosive global spreading of multidrug resistant Mycobacterium tuberculosis (Mtb) is a catastrophe, which demands an urgent need to design or develop novel/potent antitubercular agents. The Lysine/DAP biosynthetic pathway is a promising target due its specific role in cell wall and amino acid biosynthesis. Here, we report identification of potential antitubercular candidates targeting Mtb dihydrodipicolinate synthase (DHDPS) enzyme of the pathway using virtual screening protocols. In the present study, we generated three sets of drug-like molecules in order to screen potential inhibitors against Mtb drug target DHDPS. The first set of compounds was a combinatorial library, which comprised analogues of pyruvate (substrate of DHDPS). The second set of compounds consisted of pyruvate-like molecules i.e. structurally similar to pyruvate, obtained using 3D flexible similarity search against NCI and PubChem database. The third set constituted 3847 anti-infective molecules obtained from PubChem. These compounds were subjected to Lipinski's rule of drug-like five filters. Finally, three sets of drug-like compounds i.e. 4088 pyruvate analogues, 2640 pyruvate-like molecules and 1750 anti-infective molecules were docked at the active ...Continue Reading

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Citations

Sep 11, 2014·Journal of Biomolecular Structure & Dynamics·Rahul Shubhra Mandal, Santasabuj Das
Jun 21, 2019·Protein and Peptide Letters·Jian-Ping HuShan Chang

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Methods Mentioned

BETA
gene-knockout

Software Mentioned

VLifeMDS
AutoGrid
python
AutoDock
PYMOL
LeadGrow

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