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
[1]
Agyeman, A.A.; Ofori-Asenso, R. Tuberculosis-an overview. J. Public Health Emerg., 2017, 1(7), 1-11.
[5]
Velayati, A.A.; Masjedi, M.R.; Farnia, P.; Tabarsi, P.; Ghanavi, J. ZiaZarifi, A.H.; Hoffner, S.E. Emergence of new forms of totally drug-resistant tuberculosis bacilli: Super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran. Chest, 2009, 136(2), 420-425.
[6]
Kalyaanamoorthy, S.; Chen, Y-P.P. Structure-based drug design to augment hit discovery. Drug Discov. Today, 16(17-18), 831-839.
[7]
Ekins, S.; Godbole, A.A.; Keri, G.; Orfi, L.; Pato, J.; Bhat, R.S.; Verma, R.; Bradley, E.K.; Nagaraja, V. Machine learning and docking models for Mycobacterium tuberculosis topoisomerase I. Tuberculosis, 2017, 103, 52-60.
[8]
Hartman, G.D.; Egbertson, M.S.; Halczenko, W.; Laswell, W.L.; Duggan, M.E.; Smith, R.L.; Naylor, A.M.; Manno, P.D.; Lynch, R.J. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J. Med. Chem., 1992, 35(24), 4640-4642.
[9]
Vijayakrishnan, R. Structure-based drug design and modern medicine. J. Postgrad. Med., 2009, 55(4), 301.
[10]
Talele, T.T.; Khedkar, S.A.; Rigby, A.C. Successful applications of computer aided drug discovery: Moving drugs from concept to the clinic. Curr. Top. Med. Chem., 2010, 10(1), 127-141.
[11]
Van Drie, J.H. Computer-aided drug design: the next 20 years. J. Comput. Aided Mol. Des., 2007, 21(10-11), 591-601.
[12]
Ekins, S.; Freundlich, J.S.; Choi, I.; Sarker, M.; Talcott, C. Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery. Trends Microbiol., 2011, 19(2), 65-74.
[13]
Rawat, D.S. Antituberculosis drug research: A critical overview. Med. Res. Rev., 2013, 33(4), 693-764.
[14]
Njogu, P.M.; Guantai, E.M.; Pavadai, E.; Chibale, K. Computer-aided drug discovery approaches against the tropical infectious diseases malaria, tuberculosis, trypanosomiasis, and leishmaniasis. ACS Infect. Dis., 2016, 2(1), 8-31.
[15]
Swaminathan, S.; Sundaramurthi, J.C.; Palaniappan, A.N.; Narayanan, S. Recent developments in genomics, bioinformatics and drug discovery to combat emerging drug-resistant tuberculosis. Tuberculosis, 2016, 101, 31-40.
[16]
Fernandes, G.F.D.S.; Man Chin, C.; Dos Santos, J.L. Advances in drug discovery of new antitubercular multidrug-resistant compounds. Pharmaceuticals, 2017, 10(2), 51.
[17]
Zhang, W.; Pei, J.; Lai, L. Computational multitarget drug design. J. Chem. Inf. Model., 2017, 57(3), 403-412.
[18]
Khusro, A.; Aarti, C.; Barbabosa-Pliego, A.; Salem, A.Z.M. Neoteric advancement in TB drugs and an overview on the anti-tubercular role of peptides through computational approaches. Microb. Pathog., 2018, 114, 80-89.
[19]
Mdluli, K.; Spigelman, M. Novel targets for tuberculosis drug discovery. Curr. Opin. Pharmacol., 2006, 6(5), 459-467.
[20]
Scheich, C.; Szabadka, Z.; Vertessy, B.; Pütter, V.; Grolmusz, V.; Schade, M. Discovery of novel MDR-Mycobacterium tuberculosis inhibitor by new FRIGATE computational screen. PLoS One, 2011, 6(12)e28428
[21]
Billones, J.B.; Carrillo, M.C.O.; Organo, V.G.; Macalino, S.J.Y.; Sy, J.B.A.; Emnacen, I.A.; Clavio, N.A.B.; Concepcion, G.P. Toward antituberculosis drugs: In silico screening of synthetic compounds against Mycobacterium tuberculosis L, D-transpeptidase 2. Drug Des. Devel. Ther., 2016, 10, 1147-1157.
[22]
Crystal structure of Mycobacterium tuberculosis shikimate kinase
in complex with ADP and a shikimic acid derivative (PDB ID: 4BQS),http://www.rcsb.org/structure/4BQS (Accessed on
13.12.2018).
[23]
Petersen, G.O.; Saxena, S.; Renuka, J.; Soni, V.; Yogeeswari, P.; Santos, D.S.; Bizarro, C.V.; Sriram, D. Structure-based virtual screening as a tool for the identification of novel inhibitors against Mycobacterium tuberculosis 3-dehydroquinate dehydratase. J. Mol. Graph. Model., 2015, 60, 124-131.
[24]
Crystal structure of Mycobacterium tuberculosis dethiobiotin synthetase complexed with 7,8 diaminopelargonic acid carbamate;
(PDB ID: 3FMF), https://www.rcsb.org/structure/3FMF
(Accessed on 13.12.2018).
[25]
Structure of. Mycobacterium tuberculosis tryptophan synthase in
space group F222 (PDB ID: 5OCW), http://www.rcsb.org/structure/5OCW
[26]
Wang, D.; Zhu, X.; Cui, C.; Dong, M.; Jiang, H.; Li, Z.; Liu, Z.; Zhu, W.; Wang, J-G. Discovery of novel acetohydroxyacid synthase inhibitors as active agents against Mycobacterium tuberculosis by virtual screening and bioassay. J. Chem. Inf. Model., 2013, 53(2), 343-353.
[27]
Crystal structure of Mycobacterium tuberculosis glutamine synthetase
in complex with a transition state mimic (PDB ID: 2BVC), https://www.rcsb.org/structure/2BVC (Accessed on 01.10.2018).
[28]
Crystal structure of pantothenate synthetase from Mycobacterium
tuberculosis in complex with 5-Methoxy-N-(5-methylpyridin-2-
ylsulfonyl)-1H-indole-2-carboxamide (PDB ID: 3IUB), http://www.rcsb.org/structure/3IUB (Accessed on 13.12.2018)
[29]
Crystal Structure of the Class Ib Ribonucleotide Reductase R2F-2
subunit from Mycobacterium tuberculosis (PDB ID: 1UZR), https://www.rcsb.org/structure/1UZR (Accessed on 13.12.2018).
[30]
High resolution crystal structure of reductase (R) domain of nonribosomal
peptide synthetase from Mycobacterium tuberculosis
(PDB ID: 4U5Q), http://www.rcsb.org/structure/4U5Q (Accessed
on 13.12.2018).
[31]
Crystal structure of a type III polyketide synthase PKS18 from
Mycobacterium tuberculosis (PDB ID: 1TED), http://www.rcsb.org/structure/1TED (Accessed on 13.12.2018).
[32]
Crystal structure of biotin-protein ligase BirA from Mycobacterium
tuberculosis in complex with an acylsulfamide bisubstrate inhibitor
(PDB ID: 3RUX), http://www.rcsb.org/structure/3RUX (Accessed
on 13.12.2018).
[33]
Structure of mycobacterial lipoamide dehydrogenase bound to a
triazaspirodimethoxybenzoyl inhibitor (PDB ID: 3II4), http://www.rcsb.org/structure/3II4 (Accessed on 13.12.2018).
[34]
Crystal structure of the M. tuberculosis CTP synthase PyrG (apo
form) (PDB ID: 4ZDI), https://www.rcsb.org/structure/4ZDI (Accessed
on 13.12.2018).
[35]
MTB adenosine kinase in complex with gamma-Thio-ATP (PDB
ID: 4O1G), https://www.rcsb.org/structure/4o1g (Accessed on
13.12.2018).
[36]
Chiaradia, L.D.; Martins, P.G.A.; Cordeiro, M.N.S.; Guido, R.V.C.; Ecco, G.; Andricopulo, A.D.; Yunes, R.A.; Vernal, J.; Nunes, R.J.; Terenzi, H.n. Synthesis, biological evaluation, and molecular modeling of chalcone derivatives as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases (PtpA and PtpB). J. Med. Chem., 2012, 55(1), 390-402.
[37]
Crystal Structure of Protein kinase PknG from Mycobacterium
tuberculosis in Complex with Tetrahydrobenzothiophene AX20017
(PDB ID: 2PZI), https://www.rcsb.org/structure/2PZI
(Accessed on
01.10.2018).
[38]
Crystal structure of Mycobacterium tuberculosis malate synthase in
complex with 2-naphthyldiketoacid (PDB ID: 6AXB), http://www.rcsb.org/structure/6AXB (Accessed on 13.12.2018).
[39]
Structure of mycobacterial maltokinase, the missing link in the
essential GlgE-pathway (AppCp complex) (PDB ID: 4U98), https://www.rcsb.org/structure/4U98
(Accessed on 13.12.2018).
[40]
Crystal Structures of Mycobacterium tuberculosis Folylpolyglutamate
Synthase Complexed with ADP and AMPPCP (PDB ID:
2VOR), https://www.rcsb.org/structure/2VOR
(Accessed on
13.12.2018).
[41]
Crystal Structure of type II MenB from Mycobacteria tuberculosis
(PDB ID: 4QII), http://www.rcsb.org/structure/4QII
(Accessed on
13.12.2018).
[42]
Crystal structure of glucosyl-3-phosphoglycerate synthase from
Mycobacterium tuberculosis (PDB ID: 4DDZ), http://www.rcsb.org/structure/4DDZ (Accessed on 13.12.2018).
[43]
The Structure of Mycothiol Synthase in Complex with des- AcetylMycothiol and CoenzymeA (PDB ID: 2C27). http://www.rcsb.org/structure/2C27 (Accessed on 13.12.2018).
[44]
HorvaÌti. K.; Bacsa, B.; SzaboÌ, N.r.; DaÌvid, S.N.; MezoÌ, G.B.; Grolmusz, V.; VeÌrtessy, B.T.; Hudecz, F.; Bosze, S. Enhanced cellular uptake of a new, in silico identified antitubercular candidate by peptide conjugation. Bioconjugate. Chem., 2012, 23(5), 900-907.
[45]
Koch, O.; Jager, T.; Heller, K.; Khandavalli, P.C.; Pretzel, J.; Becker, K.; Flohe, Ì. L.; Selzer, P.M. Identification of M. tuberculosis thioredoxin reductase inhibitors based on high-throughput docking using constraints. J. Med. Chem., 2013, 56(12), 4849-4859.
[46]
Poyraz, O.; Jeankumar, V.U.; Saxena, S.; Schnell, R.; Haraldsson, M.; Yogeeswari, P.; Sriram, D.; Schneider, G. Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine sulfhydrylase from Mycobacterium tuberculosis. J. Med. Chem., 2013, 56(16), 6457-6466.
[47]
Hamza, A.; Wagner, J.M.; Evans, T.J.; Frasinyuk, M.S.; Kwiatkowski, S.; Zhan, C-G.; Watt, D.S.; Korotkov, K.V. Novel mycosin protease MycP1 inhibitors identified by virtual screening and 4D fingerprints. J. Chem. Inf. Model., 2014, 54(4), 1166-1173.
[48]
Choudhury, C.; Priyakumar, U.D.; Sastry, G.N. Dynamics based pharmacophore models for screening potential inhibitors of mycobacterial cyclopropane synthase. J. Chem. Inf. Model., 2015, 55(4), 848-860.
[49]
Mehra, R.; Rani, C.; Mahajan, P.; Vishwakarma, R.A.; Khan, I.A.; Nargotra, A. Computationally guided identification of novel Mycobacterium tuberculosis GlmU inhibitory leads, their optimization, and in vitro validation. ACS Comb. Sci., 2016, 18(2), 100-116.
[50]
Lele, A.C.; Raju, A.; Khambete, M.P.; Ray, M.K.; Rajan, M.G.R.; Arkile, M.A.; Jadhav, N.J.; Sarkar, D.; Degani, M.S. Design and synthesis of a focused library of diamino triazines as potential Mycobacterium tuberculosis DHFR inhibitors. ACS Med. Chem. Lett., 2015, 6(11), 1140-1144.
[51]
Pauli, I.; Dos Santos, R.N.; Rostirolla, D.C.; Martinelli, L.K.; Ducati, R.G.; Timmers, L.F.S.M.; Basso, L.A.; Santos, D.S.; Guido, R.V.C.; Andricopulo, A.D. Discovery of new inhibitors of Mycobacterium tuberculosis InhA enzyme using virtual screening and a 3D-pharmacophore-based approach. J. Chem. Inf. Model., 2013, 53(9), 2390-2401.
[52]
Purohit, R.; Rajendran, V.; Sethumadhavan, R. Relationship between mutation of serine residue at 315th position in M. tuberculosis catalase-peroxidase enzyme and Isoniazid susceptibility: An in silico analysis. J. Mol. Model., 2011, 17(4), 869-877.
[53]
Mehra, R.; Rajput, V.S.; Gupta, M.; Chib, R.; Kumar, A.; Wazir, P.; Khan, I.A.; Nargotra, A. Benzothiazole derivative as a novel Mycobacterium tuberculosis shikimate kinase inhibitor: Identification and elucidation of its allosteric mode of inhibition. J. Chem. Inf. Model., 2016, 56(5), 930-940.
[54]
Singh, N.; Tiwari, S.; Srivastava, K.K.; Siddiqi, M.I. Identification of novel inhibitors of Mycobacterium tuberculosis PknG using pharmacophore based virtual screening, docking, molecular dynamics simulation, and their biological evaluation. J. Chem. Inf. Model., 2015, 55(6), 1120-1129.
[55]
Devi, P.B.; Jogula, S.; Reddy, A.P.; Saxena, S.; Sridevi, J.P.; Sriram, D.; Yogeeswari, P. Design of novel Mycobacterium tuberculosis pantothenate synthetase inhibitors: Virtual screening, synthesis and in vitro biological activities. Mol. Inf., 2015, 34(2-3), 147-159.
[56]
Jeankumar, V.U.; Saxena, S.; Vats, R.; Reshma, R.S.; Janupally, R.; Kulkarni, P.; Yogeeswari, P.; Sriram, D. Structure-guided discovery of antitubercular agents that target the gyrase atpase domain. ChemMedChem, 2016, 11(5), 539-548.
[57]
Jose, G.; Kumara, T.H.S.; Sowmya, H.B.V.; Sriram, D.; Row, T.N.G.; Hosamani, A.A.; More, S.S.; Janardhan, B.; Harish, B.G.; Telkar, S. Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo [3, 2-c] pyridine Mannich bases. . Eur. J. Med. Chem., 2017, 131, 275-288.
[58]
Lee, Y-V.; Choi, S.B.; Wahab, H.A.; Choong, Y.S. Active site flexibility of mycobacterium tuberculosis isocitrate lyase in dimer form. J. Chem. Inf. Model., 2017, 57(9), 2351-2357.
[59]
Ekins, S.; Godbole, A.A.; Keri, G.; Orfi, L.; Pato, J.; Bhat, R.S.; Verma, R.; Bradley, E.K.; Nagaraja, V. Machine learning and docking models for Mycobacterium tuberculosis topoisomerase-I. Tuberculosis, 2017, 103, 52-60.
[60]
Kumar, M.; Vijayakrishnan, R.; Rao, G.S. In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis Dihydrofolate reductase, a potential target for anti-TB drug discovery. Mol. Divers., 2010, 14(3), 595-604.
[61]
Muddassar, M.; Jang, J.W.; Gon, H.S.; Cho, Y.S.; Kim, E.E.; Keum, K.C.; Oh, T.; Cho, S-N.; Pae, A.N. Identification of novel antitubercular compounds through hybrid virtual screening approach. Bioorg. Med. Chem., 2010, 18(18), 6914-6921.
[62]
Kinjo, T.; Koseki, Y.; Kobayashi, M.; Yamada, A.; Morita, K.; Yamaguchi, K.; Tsurusawa, R.; Gulten, G.; Komatsu, H.; Sakamoto, H. Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening. J. Chem. Inf. Model., 2013, 53(5), 1200-1212.
[63]
Blanco, B.; Prado, V.; Lence, E.; Otero, J.M.; Garcia-Doval, C.; van Raaij, M.J.; Llamas-Saiz, A.L.; Lamb, H.; Hawkins, A.R.; Gonzalez-Bello, C. Mycobacterium tuberculosis shikimate kinase inhibitors: design and simulation studies of the catalytic turnover. J. Am. Chem. Soc., 2013, 135(33), 12366-12376.
[64]
Jena, L.; Waghmare, P.; Kashikar, S.; Kumar, S.; Harinath, B.C. Computational approach to understanding the mechanism of action of isoniazid, an anti-TB drug. Int. J. Mycobacteriol., 2014, 3(4), 276-282.
[65]
Perryman, A.L.; Yu, W.; Wang, X.; Ekins, S.; Forli, S.; Li, S-G.; Freundlich, J.S.; Tonge, P.J.; Olson, A.J. A virtual screen discovers novel, fragment-sized inhibitors of Mycobacterium tuberculosis InhA. J. Chem. Inf. Model., 2015, 55(3), 645-659.
[66]
Jose, G.; Kumara, T.H.S.; Nagendrappa, G.; Sowmya, H.B.V.; Sriram, D.; Yogeeswari, P.; Sridevi, J.P.; Row, T.N.G.; Hosamani, A.A.; Ganapathy, P.S.S. Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo [1, 2-a] pyridine-2-carboxamide derivatives. Eur. J. Med. Chem., 2015, 89, 616-627.
[67]
Mujahid, M.; Yogeeswari, P.; Sriram, D.; Basavanag, U.M.V.; Diaz-Cervantes, E.; Cordoba-Bahena, L.; Robles, J.; Gonnade, R.G.; Karthikeyan, M.; Vyas, R. Spirochromone-chalcone conjugates as antitubercular agents: Synthesis, bio evaluation and molecular modeling studies. RSC Advances, 2015, 5(129), 106448-106460.
[68]
Revathi, R.; Perumal, R.V.; Pai, K.S.R.; Arunkumar, G.; Sriram, D.; Kini, S.G. Design, development, drug-likeness, and molecular docking studies of novel piperidin-4-imine derivatives as antitubercular agents. Drug Des. Devel. Ther., 2015, 9, 3779-3787.
[69]
Soni, V.; Suryadevara, P.; Sriram, D.; Kumar, S.; Nandicoori, V.K.; Yogeeswari, P.; Consortium, O. Structure-based design of diverse inhibitors of Mycobacterium tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase: Combined molecular docking, dynamic simulation, and biological activity. J. Mol. Model., 2015, 21(7), 174.
[70]
Tatar, E.; Karakus, S.; Kucukguzel, S.G.; Okullu, S.O.; Kocagöz, N.; Ünübol, N.; De Clercq, E.; Andrei, G.; Snoeck, R.; Pannecouque, C. Design, synthesis, and molecular docking studies of a conjugated thiadiazole-thiourea scaffold as antituberculosis agents. Biol. Pharm. Bull., 2016, 39(4), 502-515.
[71]
Goud, G.L.; Ramesh, S.; Ashok, D.; Reddy, V.P.; Yogeeswari, P.; Sriram, D.; Saikrishna, B.; Manga, V. Design, synthesis, molecular-docking and antimycobacterial evaluation of some novel 1, 2, 3-triazolyl xanthenones. MedChemComm, 2017, 8(3), 559-570.
[72]
Protein structure of dihydrofolate reductase of mycobacterium
tuberculosis complexed with NADPH and methotrexate (PDB ID:
1DF7), https://www.rcsb.org/structure/1DF7 (Accessed on
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).
[75]
Crystal structure of Mycobacterium tuberculosis enoyl reductase
(InhA) inhibited by 5-pentyl-2-phenoxyphenol (PDB ID: 2B36), https://www.rcsb.org/structure/2B36 (Accessed on 27.09.2018).
[76]
Crystal structure of Mycobacterium tuberculosis enoyl reductase
(INHA) complexed with N-(3-bromophenyl)-1-cyclohexyl-5-
oxopyrrolidine-3-carboxamide, refined with new ligand restraints
(PDB ID: 4TRJ), https://www.rcsb.org/structure/4TRJ
(Accessed
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).
[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).
[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).
[92]
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).
[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).
[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).
[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).
[104]
Maybridge small molecule database, https://www.maybridge.com/ portal/alias__Rainbow/lang__en/tabID__146/DesktopDefault.aspx
(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
01.10.2018)
[109]
Crystal structure of Mycobacterium tuberculosis enoyl reductase
(INHA) complexed with 1-cyclohexyl-n-(3,5-dichlorophenyl)-5-
oxopyrrolidine-3-carboxamide (PDB ID: 4TZK), https://www.rcsb.org/structure/4TZK
(Accessed on 01.10.2018)
[110]
Crystal structure of GlmU from Mycobacterium tuberculosis in
complex with Coenzyme A, glucosamine 1-phosphate and uridinediphosphate-
N-acetylglucosamine (PDB ID: 3ST8), https://www.rcsb.org/structure/3ST8
(Accessed on 02.10.2018).
[111]
Desmond software. https://www.deshawresearch.com/-resources_ desmond.html
(Accessed on 01.10.2018)
[112]
Crystal Structure of. M. tuberculosis LD-transpeptidase type 2
complexed with a peptidoglycan fragment (PDB ID: 3TUR), https://www.rcsb.org/structure/3TUR
(Accessed on 01.10.2018).
[113]
CHARMm-based DOCKER (CDOCKER) software. https://www.charmm.org/charmm/?CFID=1f49ab54-f933-447b-a072-0e2cac9fc555&CFTOKEN=0
(Accessed on 01.10.2018).
[114]
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).
[116]
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).
[119]
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)
[120]
Crystal structure of Mycobacterium tuberculosis Topoisomerase I
(PDB ID: 5D5H), https://www.rcsb.org/structure/5D5H
(Accessed
on 01.10.2018).
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