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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Review Article

Computational Approaches as Rational Decision Support Systems for Discovering Next-Generation Antitubercular Agents: Mini-Review

Author(s): Rahul Balasaheb Aher and Kunal Roy*

Volume 15 , Issue 5 , 2019

Page: [369 - 383] Pages: 15

DOI: 10.2174/1573409915666190130153214

Price: $65


Tuberculosis, malaria, dengue, chikungunya, leishmaniasis etc. are a large group of neglected tropical diseases that prevail in tropical and subtropical countries, affecting one billion people every year. Minimal funding and grants for research on these scientific problems challenge many researchers to find a different way to reduce the extensive time and cost involved in the drug discovery cycle of these problems. Computer-aided drug design techniques have already been proved successful in the discovery of new molecules rationally by reducing the time and cost involved in the development of drugs. In the current minireview, we are highlighting on the molecular modeling studies published during 2010-2018 for target specific antitubercular agents. This review includes the studies of Structure-Based (SB) and Ligand-Based (LB) modeling and those involving Machine Learning (ML) techniques against different antitubercular targets such as dihydrofolate reductase (DHFR), enoyl Acyl Carrier Protein (ACP) reductase (InhA), catalase-peroxidase (KatG), enzyme antigen 85C, protein tyrosine phosphatases (PtpA and PtpB), dUTPase, thioredoxin reductase (MtTrxR), etc. The information presented in this review will help the researchers to get acquainted with the recent progress in the modeling studies of antitubercular agents.

Keywords: Neglected diseases, antitubercular targets, structure-based, ligand-based, machine learning, thioredoxin reductase.

Graphical Abstract
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Structure of. Mycobacterium tuberculosis type II dehydroquinase complexed with (1R,4S,5R)-1,4,5-trihydroxy-3-((5-methylbenzo(b) thiophen-2-yl)methoxy)cyclohex-2-enecarboxylate (PDB ID: 2Y71), (Accessed on 01.10.2018)
Crystal structure of Mycobacterium tuberculosis enoyl reductase (INHA) complexed with 1-cyclohexyl-n-(3,5-dichlorophenyl)-5- oxopyrrolidine-3-carboxamide (PDB ID: 4TZK), (Accessed on 01.10.2018)
Crystal structure of GlmU from Mycobacterium tuberculosis in complex with Coenzyme A, glucosamine 1-phosphate and uridinediphosphate- N-acetylglucosamine (PDB ID: 3ST8), (Accessed on 02.10.2018).
Desmond software. desmond.html (Accessed on 01.10.2018)
Crystal Structure of. M. tuberculosis LD-transpeptidase type 2 complexed with a peptidoglycan fragment (PDB ID: 3TUR), (Accessed on 01.10.2018).
CHARMm-based DOCKER (CDOCKER) software. (Accessed on 01.10.2018).
Shikimate kinase from Mycobacterium tuberculosis in complex with MgATP, open LID (conf. B) (PDB ID: 2IYW), (Accessed on 01.10.2018).
Crystal structures of the quinone oxidoreductase from thermus thermophilus HB8 and its complex with NADPH (PDB ID: 1IYZ), (Accessed on 01.10.2018).
Optimisation of pyrroleamides as mycobacterial GyrB ATPase inhibitors: Structure Activity Relationship and in vivo efficacy in the mouse model of tuberculosis (PDB ID: 4BAE), (Accessed on 01.10.2018).
Crystal structure of isocitrate lyase from mycobacterium tuberculosis (PDB ID: 1F61), (Accessed on 01.10.2018).
Crystal structure of isocitrate lyase: Nitropropionate: Glyoxylate complex from mycobacterium tuberculosis (PDB ID: 1F8I ), (Accessed on 01.10.2018).
Crystal Structure of the C123S 2-Methylisocitrate Lyase Mutant from Escherichia coli in complex with the inhibitor isocitrate (PDB ID: 1XG4), (Accessed on 01.10.2018)
Crystal structure of Mycobacterium tuberculosis Topoisomerase I (PDB ID: 5D5H), (Accessed on 01.10.2018).

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