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

Rahul    Balasaheb    Aher; Kunal       Roy
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.
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Graphical Abstract

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[72] 
 Protein structure of dihydrofolate reductase of mycobacterium
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02.1018).
[73] 
 Accelrys Discovery studio software (DS 1.7), http://www.3dsbiovia.com/products/collaborative-science/biovia-discovery-studio/ (accessed on 02.10.2018).
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 Chemdiv database, http://www.chemdiv.com/ (Accessed on
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 Crystal structure of Mycobacterium tuberculosis enoyl reductase
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[76] 
 Crystal structure of Mycobacterium tuberculosis enoyl reductase
(INHA) complexed with N-(3-bromophenyl)-1-cyclohexyl-5-
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on 27.09.2018).
[77] 
 Enoyl acyl carrier protein reductase InhA in complex with N-(4-
methylbenzoyl)-4-benzylpiperidine (PDB ID: 2NSD), https://www.rcsb.org/structure/2NSD (Accessed on 27.09.2018).
[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).
[81] 
 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).
[84] 
 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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Sander, T.; Freyss, J.; von Korff, M.; Reich, J.R.; Rufener, C. OSIRIS, an entirely in-house developed drug discovery informatics system. J. Chem. Inf. Model.,  2009, 49(2), 232-246.
[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).
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 ChEMBL database, https://www.ebi.ac.uk/chembl/ (Accessed on
01.10.2018).
[107] 
  Crystal structure of pantothenate synthetase in complex with 2-(2-
(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-
yl)acetic acid (PDB ID: 3IVX),https://www.rcsb.org/structure/3IVX (Accessed on 01.10.2018)
[108] 
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), https://www.rcsb.org/structure/2Y71
                   (Accessed on
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DOI https://dx.doi.org/10.2174/1573409915666190130153214	Print ISSN 1573-4099
Publisher Name Bentham Science Publisher	Online ISSN 1875-6697
Current Computer-Aided Drug Design

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

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