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Current Computer-Aided Drug Design

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

DOI: 10.2174/1573409915666190130153214

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

Page: [369 - 383] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

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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Chemdiv database, http://www.chemdiv.com/ (Accessed on 27.09.2018).
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[76]
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[78]
Crystal structure of InhA bound to triclosan derivative (PDB ID: 3FNG), https://www.rcsb.org/structure/3FNG (Accessed on 27.09.2018).
[79]
Glide module of Schrodinger, https://www.schrodinger.com/ (Accessed on 27.09.2018).
[80]
ZINC database, http://zinc.docking.org/ (Accessed on 27.09.2018).
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Crystal structure of Mycobacterium tuberculosis Low Molecular Protein Tyrosine Phosphatase (MPtpA) at 1.9A resolution (PDB ID: 1U2P), https://www.rcsb.org/structure/1U2P (accessed on 27.09.2018).
[82]
Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS (PDB ID: 2OZ5), https://www.rcsb.org/structure/2OZ5 (accessed on 27.09.2018).
[83]
GOLD software. https://www.ccdc.cam.ac.uk/products/life_scien ces/gold/ (Accessed on 27.09.2018).
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ChemBridge database, https://www.chembridge.com/screening_ libraries/ (Accessed on 01.10.2018)
[85]
DOCK software. http://dock.compbio.ucsf.edu/ (Accessed on 27.09.2018).
[86]
Crystal Structure of Yeast Acetohydroxyacid Synthase in Complex with a Sulfonylurea Herbicide, Chlorimuron Ethyl (PDB ID: 1N0H), https://www.rcsb.org/structure/1N0H (Accessed on 27.09.2018).
[87]
2.1 A Resolution crystal structure of O-Acetylserine Sulfhydrylase (OASS) holoenzyme from mycobacterium tuberculosis in complex with the inhibitory peptide DFSI (PDB ID: 2Q3C), https://www.rcsb.org/structure/2Q3C (Accessed on 27.09.2018).
[88]
Asinex database, www.asinex.com (accessed on 27.09.2018).
[89]
Phase module of Schrodinger, https://www.schrodinger.com/phase (Accessed on 01.10.2018).
[90]
FlexX software. https://www.biosolveit.de/FlexX/ (Accessed on 01.10.2018).
[91]
Surflex-Dock software. http://www.jainlab.org/downloads.html (Accessed on 29.09.2018).
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[93]
Shikimate kinase from Mycobacterium tuberculosis in complex with shikimate and ADP (PDB ID: 2IYQ), https://www.rcsb.org/structure/2IYQ (Accessed on 29.09.2018).
[94]
Shikimate kinase from Mycobacterium tuberculosis in complex with shikimate-3-phosphate and ADP (PDB ID: 2IYZ), https://www.rcsb.org/structure/2IYZ (Accessed on 29.09.2018).
[95]
AMBER software. http://ambermd.org/ (Accessed on 29.09.2018).
[96]
Structure of a serine protease MycP1, an essential component of the type VII (ESX-1) secretion system (PDB ID: 4HVL), https://www.rcsb.org/structure/4HVL (Accessed on 29.09.2018).
[97]
Modeller software. https://salilab.org/modeller/ (Accessed on 29.09.2018).
[98]
Autodock software. http://autodock.scripps.edu/ (Accessed on 29.09.2018).
[99]
Crystal structure of M. tuberculosis InhA inhibited by PT70 (PDB ID: 2X22), https://www.rcsb.org/structure/2X22 (Accessed on 29.09.2018)
[100]
Dihydrofolate reductase of mycobacterium tuberculosis complexed with NADPH and trimethoprim (PDB ID: 1DG5), https://www.rcsb.org/structure/1DG5 (Accessed on 29.09.2018).
[101]
MOE software. https://www.chemcomp.com/MOE-Molecular_Operating_Environment.htm (29.09.2018).
[102]
Long fatty acid chain enoyl-ACP reductase (inha) in complex with an isonicotinic-acyl-NADH inhibitor (PDB ID: 1ZID), https://www.rcsb.org/structure/1ZID (Accessed on 01.10.2018).
[103]
Sybyl-2.0 software, http://www.tripossoftware.com (Accessed on 01.10.2018).
[104]
Maybridge small molecule database, https://www.maybridge.com/ portal/alias__Rainbow/lang__en/tabID__146/DesktopDefault.aspx (accessed on 01.10.2018).
[105]
Gromac software. http://www.gromacs.org/ (Accessed on 01.10.2018).
[106]
ChEMBL database, https://www.ebi.ac.uk/chembl/ (Accessed on 01.10.2018).
[107]
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Shikimate kinase from Mycobacterium tuberculosis in complex with MgATP, open LID (conf. B) (PDB ID: 2IYW), https://www.rcsb.org/structure/2IYW (Accessed on 01.10.2018).
[115]
Crystal structures of the quinone oxidoreductase from thermus thermophilus HB8 and its complex with NADPH (PDB ID: 1IYZ), https://www.rcsb.org/structure/1IYZ (Accessed on 01.10.2018).
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Optimisation of pyrroleamides as mycobacterial GyrB ATPase inhibitors: Structure Activity Relationship and in vivo efficacy in the mouse model of tuberculosis (PDB ID: 4BAE), https://www.rcsb.org/structure/4BAE (Accessed on 01.10.2018).
[117]
Crystal structure of isocitrate lyase from mycobacterium tuberculosis (PDB ID: 1F61), https://www.rcsb.org/structure/1F61 (Accessed on 01.10.2018).
[118]
Crystal structure of isocitrate lyase: Nitropropionate: Glyoxylate complex from mycobacterium tuberculosis (PDB ID: 1F8I ), https://www.rcsb.org/structure/1F8I (Accessed on 01.10.2018).
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Crystal Structure of the C123S 2-Methylisocitrate Lyase Mutant from Escherichia coli in complex with the inhibitor isocitrate (PDB ID: 1XG4), https://www.rcsb.org/structure/1XG4 (Accessed on 01.10.2018)
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Crystal structure of Mycobacterium tuberculosis Topoisomerase I (PDB ID: 5D5H), https://www.rcsb.org/structure/5D5H (Accessed on 01.10.2018).