Docking Screens for Novel Ligands Conferring New Biology

Journal of Medicinal Chemistry

Volumn 59, Issue 9, 2016, Pages 4103-4120

  Irwin, John J ^a   Shoichet, Brian K ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA LACTAMASE INHIBITOR; RAS PROTEIN; SEROTONIN RECEPTOR; LIGAND;

BINDING AFFINITY; BINDING SITE; COLLOID; COMBINATORIAL LIBRARY; CONFORMATIONAL TRANSITION; COVALENT BOND; CRYSTAL STRUCTURE; DRUG IMPURITY; HIGH THROUGHPUT SCREENING; HUMAN; IN VIVO STUDY; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR LIBRARY; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN TARGETING; PROTON TRANSPORT; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; SPECTROSCOPY; TAUTOMERIZATION; THERMODYNAMICS; UPREGULATION; X RAY CRYSTALLOGRAPHY;

LIGANDS; MOLECULAR DOCKING SIMULATION;

EID: 84969545588     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b02008     Document Type: Review

References (256)

1. Beddell, C. R.; Goodford, P. J.; Norrington, F. E.; Wilkinson, S.; Wootton, R. Compounds designed to fit a site of known structure in human haemoglobin Br. J. Pharmacol. 1976, 57, 201-209 10.1111/j.1476-5381.1976.tb07468.x
2. Cohen, S. S. A strategy for the chemotherapy of infectious disease Science 1977, 197, 431-432 10.1126/science.195340
3. Shoichet, B. K.; Kobilka, B. K. Structure-based drug screening for G-protein-coupled receptors Trends Pharmacol. Sci. 2012, 33, 268-272 10.1016/j.tips.2012.03.007
4. Mittl, P. R.; Grutter, M. G. Opportunities for structure-based design of protease-directed drugs Curr. Opin. Struct. Biol. 2006, 16, 769-775 10.1016/j.sbi.2006.10.014
5. von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R. Rational design of potent sialidase-based inhibitors of influenza virus replication Nature 1993, 363, 418-423 10.1038/363418a0
6. Varney, M. D.; Marzoni, G. P.; Palmer, C. L.; Deal, J. G.; Webber, S.; Welsh, K. M.; Bacquet, R. J.; Morse, C. A.; Booth, C. L. J.; Herrmann, S. M.; Howland, E. F.; Ward, R. W.; White, J. Crystal-structure-based design and synthesis of Benz[cd]indole-containing inhibitors of thymidylate synthase J. Med. Chem. 1992, 35, 663-676 10.1021/jm00082a006
7. Feng, J.; Zhang, Z.; Wallace, M. B.; Stafford, J. A.; Kaldor, S. W.; Kassel, D. B.; Navre, M.; Shi, L.; Skene, R. J.; Asakawa, T.; Takeuchi, K.; Xu, R.; Webb, D. R.; Gwaltney, S. L., 2nd Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV J. Med. Chem. 2007, 50, 2297-2300 10.1021/jm070104l
8. Sicheri, F.; Moarefi, I.; Kuriyan, J. Crystal structure of the Src family tyrosine kinase Hck Nature 1997, 385, 602-609 10.1038/385602a0
9. Rognan, D. Proteome-scale docking: myth and reality Drug Discovery Today: Technol. 2013, 10, e403-409 10.1016/j.ddtec.2013.01.003
10. Richter, L.; de Graaf, C.; Sieghart, W.; Varagic, Z.; Morzinger, M.; de Esch, I. J.; Ecker, G. F.; Ernst, M. Diazepam-bound GABAA receptor models identify new benzodiazepine binding-site ligands Nat. Chem. Biol. 2012, 8, 455-464 10.1038/nchembio.917
11. Min, J.; Lin, D.; Zhang, Q.; Zhang, J.; Yu, Z. Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU Eur. J. Med. Chem. 2012, 53C, 150-158 10.1016/j.ejmech.2012.03.051
12. Lavecchia, A.; Di Giovanni, C.; Pesapane, A.; Montuori, N.; Ragno, P.; Martucci, N. M.; Masullo, M.; De Vendittis, E.; Novellino, E. Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening J. Med. Chem. 2012, 55, 4142-4158 10.1021/jm201624h
13. da Silva, F. M.; dos Santos, J. C.; Campos, J. L.; Mafud, A. C.; Polikarpov, I.; Figueira, A. C.; Nascimento, A. S. Structure-based identification of novel PPAR gamma ligands Bioorg. Med. Chem. Lett. 2013, 23, 5795-5802 10.1016/j.bmcl.2013.09.010
14. Lee, H. J.; Bao, J.; Miller, A.; Zhang, C.; Wu, J.; Baday, Y. C.; Guibao, C.; Li, L.; Wu, D.; Zheng, J. J. Structure-based discovery of novel small molecule Wnt signaling inhibitors by targeting the cysteine-rich domain of frizzled J. Biol. Chem. 2015, 290, 30596-30606 10.1074/jbc.M115.673202
15. Harikishore, A.; Li, E.; Lee, J. J.; Cho, N. J.; Yoon, H. S. Combination of pharmacophore hypothesis and molecular docking to identify novel inhibitors of HCV NS5B polymerase Mol. Diversity 2015, 19, 529-539 10.1007/s11030-015-9591-5
16. Zhu, J.; Mishra, R. K.; Schiltz, G. E.; Makanji, Y.; Scheidt, K. A.; Mazar, A. P.; Woodruff, T. K. Virtual high-throughput screening to identify novel activin antagonists J. Med. Chem. 2015, 58, 5637-5648 10.1021/acs.jmedchem.5b00753
17. Soni, V.; Suryadevara, P.; Sriram, D.; Consortium, O.; Kumar, S.; Nandicoori, V. K.; Yogeeswari, P. 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, 174 10.1007/s00894-015-2704-3
18. Ruggeri, C.; Drinkwater, N.; Sivaraman, K. K.; Bamert, R. S.; McGowan, S.; Paiardini, A. Identification and validation of a potent dual inhibitor of the P. falciparum M1 and M17 aminopeptidases using virtual screening PLoS One 2015, 10, e0138957 10.1371/journal.pone.0138957
19. Schmidt, D.; Bernat, V.; Brox, R.; Tschammer, N.; Kolb, P. Identifying modulators of CXC receptors 3 and 4 with tailored selectivity using multi-target docking ACS Chem. Biol. 2015, 10, 715-724 10.1021/cb500577j
20. 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, 645-659 10.1021/ci500672v
21. Li, J.; Liu, X.; Li, S.; Wang, Y.; Zhou, N.; Luo, C.; Luo, X.; Zheng, M.; Jiang, H.; Chen, K. Identification of novel small molecules as inhibitors of hepatitis C virus by structure-based virtual screening Int. J. Mol. Sci. 2013, 14, 22845-22856 10.3390/ijms141122845
22. Soelaiman, S.; Wei, B. Q.; Bergson, P.; Lee, Y. S.; Shen, Y.; Mrksich, M.; Shoichet, B. K.; Tang, W. J. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough J. Biol. Chem. 2003, 278, 25990-25997 10.1074/jbc.M301232200
23. Iwata, Y.; Arisawa, M.; Hamada, R.; Kita, Y.; Mizutani, M. Y.; Tomioka, N.; Itai, A.; Miyamoto, S. Discovery of novel aldose reductase inhibitors using a protein structure-based approach: 3D-database search followed by design and synthesis J. Med. Chem. 2001, 44, 1718-1728 10.1021/jm000483h
24. Enyedy, I. J.; Ling, Y.; Nacro, K.; Tomita, Y.; Wu, X.; Cao, Y.; Guo, R.; Li, B.; Zhu, X.; Huang, Y.; Long, Y. Q.; Roller, P. P.; Yang, D.; Wang, S. Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening J. Med. Chem. 2001, 44, 4313-4324 10.1021/jm010016f
25. Pang, Y. P.; Xu, K.; Kollmeyer, T. M.; Perola, E.; McGrath, W. J.; Green, D. T.; Mangel, W. F. Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases FEBS Lett. 2001, 502, 93-97 10.1016/S0014-5793(01)02672-2
26. Honma, T.; Hayashi, K.; Aoyama, T.; Hashimoto, N.; Machida, T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.; Suzuki-Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Morishima, H. Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design J. Med. Chem. 2001, 44, 4615-4627 10.1021/jm0103256
27. Schapira, M.; Raaka, B. M.; Samuels, H. H.; Abagyan, R. In silico discovery of novel Retinoic Acid Receptor agonist structures BMC Struct. Biol. 2001, 1, 1 10.1186/1472-6807-1-1
28. Freymann, D. M.; Wenck, M. A.; Engel, J. C.; Feng, J.; Focia, P. J.; Eakin, A. E.; Craig, S. P. Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi Chem. Biol. 2000, 7, 957-968 10.1016/S1074-5521(00)00045-4
29. Paiva, A. M.; Vanderwall, D. E.; Blanchard, J. S.; Kozarich, J. W.; Williamson, J. M.; Kelly, T. M. Inhibitors of dihydrodipicolinate reductase, a key enzyme of the diaminopimelate pathway of Mycobacterium tuberculosis Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol. 2001, 1545, 67-77 10.1016/S0167-4838(00)00262-4
30. Ragno, R.; Mai, A.; Massa, S.; Cerbara, I.; Valente, S.; Bottoni, P.; Scatena, R.; Jesacher, F.; Loidl, P.; Brosch, G. 3-(4-Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 3. Discovery of novel lead compounds through structure-based drug design and docking studies J. Med. Chem. 2004, 47, 1351-1359 10.1021/jm031036f
31. Park, H.; Hwang, K. Y.; Oh, K. H.; Kim, Y. H.; Lee, J. Y.; Kim, K. Discovery of novel alpha-glucosidase inhibitors based on the virtual screening with the homology-modeled protein structure Bioorg. Med. Chem. 2008, 16, 284-292 10.1016/j.bmc.2007.09.036
32. Ostrov, D. A.; Hernandez Prada, J. A.; Corsino, P. E.; Finton, K. A.; Le, N.; Rowe, T. C. Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening Antimicrob. Agents Chemother. 2007, 51, 3688-3698 10.1128/AAC.00392-07
33. Raboisson, P.; Desjarlais, R. L.; Reed, R.; Lattanze, J.; Chaikin, M.; Manthey, C. L.; Tomczuk, B. E.; Marugan, J. J. Identification of novel short chain 4-substituted indoles as potent alphavbeta3 antagonist using structure-based drug design Eur. J. Med. Chem. 2007, 42, 334-343 10.1016/j.ejmech.2006.10.015
34. Wang, J. G.; Xiao, Y. J.; Li, Y. H.; Ma, Y.; Li, Z. M. Identification of some novel AHAS inhibitors via molecular docking and virtual screening approach Bioorg. Med. Chem. 2007, 15, 374-380 10.1016/j.bmc.2006.09.050
35. Foloppe, N.; Fisher, L. M.; Howes, R.; Potter, A.; Robertson, A. G.; Surgenor, A. E. Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening Bioorg. Med. Chem. 2006, 14, 4792-4802 10.1016/j.bmc.2006.03.021
36. Cherkasov, A.; Shi, Z.; Fallahi, M.; Hammond, G. L. Successful in silico discovery of novel nonsteroidal ligands for human sex hormone binding globulin J. Med. Chem. 2005, 48, 3203-3213 10.1021/jm049087f
37. Huentelman, M. J.; Zubcevic, J.; Hernandez Prada, J. A.; Xiao, X.; Dimitrov, D. S.; Raizada, M. K.; Ostrov, D. A. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor Hypertension 2004, 44, 903-906 10.1161/01.HYP.0000146120.29648.36
38. Mizutani, M. Y.; Itai, A. Efficient method for high-throughput virtual screening based on flexible docking: discovery of novel acetylcholinesterase inhibitors J. Med. Chem. 2004, 47, 4818-4828 10.1021/jm030605g
39. Chandra, N.; Bhagavat, R.; Sharma, E.; Sreekanthreddy, P.; Somasundaram, K. Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/NMPRTase for glioma therapy J. Clin. Bioinf. 2011, 1, 5 10.1186/2043-9113-1-5
40. Xu, M.; Unzue, A.; Dong, J.; Spiliotopoulos, D.; Nevado, C.; Caflisch, A. Discovery of CREBBP bromodomain inhibitors by high-throughput docking and hit optimization guided by molecular dynamics J. Med. Chem. 2016, 59, 1340-1349 10.1021/acs.jmedchem.5b00171
41. Wang, L.; Yang, C.; Lu, W.; Liu, L.; Gao, R.; Liao, S.; Zhao, Z.; Zhu, L.; Xu, Y.; Li, H.; Huang, J.; Zhu, W. Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening Bioorg. Med. Chem. Lett. 2013, 23, 3496-3499 10.1016/j.bmcl.2013.04.048
42. Heusser, S. A.; Howard, R. J.; Borghese, C. M.; Cullins, M. A.; Broemstrup, T.; Lee, U. S.; Lindahl, E.; Carlsson, J.; Harris, R. A. Functional validation of virtual screening for novel agents with general anesthetic action at ligand-gated ion channels Mol. Pharmacol. 2013, 84, 670-678 10.1124/mol.113.087692
43. Zhao, H.; Gartenmann, L.; Dong, J.; Spiliotopoulos, D.; Caflisch, A. Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking Bioorg. Med. Chem. Lett. 2014, 24, 2493-2496 10.1016/j.bmcl.2014.04.017
44. Kouskoumvekaki, I.; Petersen, R. K.; Fratev, F.; Taboureau, O.; Nielsen, T. E.; Oprea, T. I.; Sonne, S. B.; Flindt, E. N.; Jonsdottir, S. O.; Kristiansen, K. Discovery of a novel selective PPARgamma ligand with partial agonist binding properties by integrated in silico/in vitro work flow J. Chem. Inf. Model. 2013, 53, 923-937 10.1021/ci3006148
45. Xu, L.; Li, C. L.; Olson, A. J.; Wilson, I. A. Crystal structure of avian aminoimidazole-4-carboxamide ribonucleotide transformylase in complex with a novel non-folate inhibitor identified by virtual ligand screening J. Biol. Chem. 2004, 279, 50555-50565 10.1074/jbc.M406801200
46. Pierce, A. C.; Jacobs, M.; Stuver-Moody, C. Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase J. Med. Chem. 2008, 51, 1972-1975 10.1021/jm701248t
47. Powers, R. A.; Morandi, F.; Shoichet, B. K. Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase Structure (Oxford, U. K.) 2002, 10, 1013-1023 10.1016/S0969-2126(02)00799-2
48. Babaoglu, K.; Simeonov, A.; Irwin, J. J.; Nelson, M. E.; Feng, B.; Thomas, C. J.; Cancian, L.; Costi, M. P.; Maltby, D. A.; Jadhav, A.; Inglese, J.; Austin, C. P.; Shoichet, B. K. Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase J. Med. Chem. 2008, 51, 2502-2511 10.1021/jm701500e
49. Wacker, D.; Fenalti, G.; Brown, M. A.; Katritch, V.; Abagyan, R.; Cherezov, V.; Stevens, R. C. Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography J. Am. Chem. Soc. 2010, 132, 11443-11445 10.1021/ja105108q
50. Ferreira, R. S.; Simeonov, A.; Jadhav, A.; Eidam, O.; Mott, B. T.; Keiser, M. J.; McKerrow, J. H.; Maloney, D. J.; Irwin, J. J.; Shoichet, B. K. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors J. Med. Chem. 2010, 53, 4891-4905 10.1021/jm100488w
51. Chen, Y.; Shoichet, B. K. Molecular docking and ligand specificity in fragment-based inhibitor discovery Nat. Chem. Biol. 2009, 5, 358-364 10.1038/nchembio.155
52. Teotico, D. G.; Babaoglu, K.; Rocklin, G. J.; Ferreira, R. S.; Giannetti, A. M.; Shoichet, B. K. Docking for fragment inhibitors of AmpC beta-lactamase Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 7455-7460 10.1073/pnas.0813029106
53. Merski, M.; Shoichet, B. K. The impact of introducing a histidine into an apolar cavity site on docking and ligand recognition J. Med. Chem. 2013, 56, 2874-2884 10.1021/jm301823g
54. Barelier, S.; Boyce, S. E.; Fish, I.; Fischer, M.; Goodin, D. B.; Shoichet, B. K. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities PLoS One 2013, 8, e69153 10.1371/journal.pone.0069153
55. Li, Y.; Kim, D. J.; Ma, W.; Lubet, R. A.; Bode, A. M.; Dong, Z. Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures J. Chem. Inf. Model. 2011, 51, 2904-2914 10.1021/ci200257b
56. Akula, N.; Zheng, H.; Han, F. Q.; Wang, N. Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design Bioorg. Med. Chem. Lett. 2011, 21, 4183-4188 10.1016/j.bmcl.2011.05.086
57. Chen, Y.; Fang, L.; Peng, S.; Liao, H.; Lehmann, J.; Zhang, Y. Discovery of a novel acetylcholinesterase inhibitor by structure-based virtual screening techniques Bioorg. Med. Chem. Lett. 2012, 22, 3181-3187 10.1016/j.bmcl.2012.03.046
58. Ji, X.; Zheng, Y.; Wang, W.; Sheng, J.; Hao, J.; Sun, M. Virtual screening of novel reversible inhibitors for marine alkaline protease MP J. Mol. Graphics Modell. 2013, 46, 125-131 10.1016/j.jmgm.2013.10.004
59. Kang, H. J.; Park, H. J. In silico identification of novel ligands for G-quadruplex in the c-MYC promoter J. Comput.-Aided Mol. Des. 2015, 29, 339-348 10.1007/s10822-014-9826-z
60. Zhao, C.; Yang, S. H.; Khadka, D. B.; Jin, Y.; Lee, K. T.; Cho, W. J. Computer-aided discovery of aminopyridines as novel JAK2 inhibitors Bioorg. Med. Chem. 2015, 23, 985-995 10.1016/j.bmc.2015.01.016
61. Lindert, S.; Tallorin, L.; Nguyen, Q. G.; Burkart, M. D.; McCammon, J. A. In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors J. Comput.-Aided Mol. Des. 2015, 29, 79-87 10.1007/s10822-014-9806-3
62. Li, S.; Sun, X.; Zhao, H.; Tang, Y.; Lan, M. Discovery of novel EGFR tyrosine kinase inhibitors by structure-based virtual screening Bioorg. Med. Chem. Lett. 2012, 22, 4004-4009 10.1016/j.bmcl.2012.04.092
63. Fang, J.; Yang, R.; Gao, L.; Yang, S.; Pang, X.; Li, C.; He, Y.; Liu, A. L.; Du, G. H. Consensus models for CDK5 inhibitors in silico and their application to inhibitor discovery Mol. Diversity 2015, 19, 149-162 10.1007/s11030-014-9561-3
64. Liu, X.; Dong, G.; Zhang, J.; Qi, J.; Zheng, C.; Zhou, Y.; Zhu, J.; Sheng, C.; Lu, J. Discovery of novel human acrosin inhibitors by virtual screening J. Comput.-Aided Mol. Des. 2011, 25, 977-985 10.1007/s10822-011-9476-3
65. Kokkonen, P.; Kokkola, T.; Suuronen, T.; Poso, A.; Jarho, E.; Lahtela-Kakkonen, M. Virtual screening approach of sirtuin inhibitors results in two new scaffolds Eur. J. Pharm. Sci. 2015, 76, 27-32 10.1016/j.ejps.2015.04.025
66. Roughley, S. D.; Hubbard, R. E. How well can fragments explore accessed chemical space? A case study from heat shock protein 90 J. Med. Chem. 2011, 54, 3989-4005 10.1021/jm200350g
67. Doman, T. N.; McGovern, S. L.; Witherbee, B. J.; Kasten, T. P.; Kurumbail, R.; Stallings, W. C.; Connolly, D. T.; Shoichet, B. K. Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B J. Med. Chem. 2002, 45, 2213-2221 10.1021/jm010548w
68. Feng, B. Y.; Simeonov, A.; Jadhav, A.; Babaoglu, K.; Inglese, J.; Shoichet, B. K.; Austin, C. P. A high-throughput screen for aggregation-based inhibition in a large compound library J. Med. Chem. 2007, 50, 2385-2390 10.1021/jm061317y
69. Jadhav, A.; Ferreira, R. S.; Klumpp, C.; Mott, B. T.; Austin, C. P.; Inglese, J.; Thomas, C. J.; Maloney, D. J.; Shoichet, B. K.; Simeonov, A. Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease J. Med. Chem. 2010, 53, 37-51 10.1021/jm901070c
70. Forli, S. Charting a Path to Success in Virtual Screening Molecules 2015, 20, 18732-18758 10.3390/molecules201018732
71. Spyrakis, F.; Cavasotto, C. N. Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description Arch. Biochem. Biophys. 2015, 583, 105-119 10.1016/j.abb.2015.08.002
72. Ferreira, L. G.; Dos Santos, R. N.; Oliva, G.; Andricopulo, A. D. Molecular docking and structure-based drug design strategies Molecules 2015, 20, 13384-13421 10.3390/molecules200713384
73. Cerqueira, N. M.; Gesto, D.; Oliveira, E. F.; Santos-Martins, D.; Bras, N. F.; Sousa, S. F.; Fernandes, P. A.; Ramos, M. J. Receptor-based virtual screening protocol for drug discovery Arch. Biochem. Biophys. 2015, 582, 56-67 10.1016/j.abb.2015.05.011
74. Kumalo, H. M.; Bhakat, S.; Soliman, M. E. Theory and applications of covalent docking in drug discovery: merits and pitfalls Molecules 2015, 20, 1984-2000 10.3390/molecules20021984
75. Webb, B.; Sali, A. Protein structure modeling with MODELLER Methods Mol. Biol. 2014, 1137, 1-15 10.1007/978-1-4939-0366-5-1
76. Pieper, U.; Webb, B. M.; Dong, G. Q.; Schneidman-Duhovny, D.; Fan, H.; Kim, S. J.; Khuri, N.; Spill, Y. G.; Weinkam, P.; Hammel, M.; Tainer, J. A.; Nilges, M.; Sali, A. ModBase, a database of annotated comparative protein structure models and associated resources Nucleic Acids Res. 2014, 42, D336-346 10.1093/nar/gkt1144
77. Fan, H.; Irwin, J. J.; Sali, A. Virtual ligand screening against comparative protein structure models Methods Mol. Biol. (N. Y., NY, U. S.) 2012, 819, 105-126 10.1007/978-1-61779-465-0-8
78. Huang, N.; Shoichet, B. K. Exploiting ordered waters in molecular docking J. Med. Chem. 2008, 51, 4862-4865 10.1021/jm8006239
79. Jain, A. N. Virtual screening in lead discovery and optimization Curr. Opin. Drug Discovery Dev. 2004, 7, 396-403
80. Verdonk, M. L.; Chessari, G.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Nissink, J. W.; Taylor, R. D.; Taylor, R. Modeling water molecules in protein-ligand docking using GOLD J. Med. Chem. 2005, 48, 6504-6515 10.1021/jm050543p
81. Mysinger, M. M.; Carchia, M.; Irwin, J. J.; Shoichet, B. K. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking J. Med. Chem. 2012, 55, 6582-6594 10.1021/jm300687e
82. Carr, R. A.; Congreve, M.; Murray, C. W.; Rees, D. C. Fragment-based lead discovery: leads by design Drug Discovery Today 2005, 10, 987-992 10.1016/S1359-6446(05)03511-7
83. Oprea, T. I.; Davis, A. M.; Teague, S. J.; Leeson, P. D. Is there a difference between leads and drugs? A historical perspective J. Chem. Inf. Model. 2001, 41, 1308-1315 10.1021/ci010366a
84. Milletti, F.; Hermann, J. C. Targeted kinase selectivity from kinase profiling data ACS Med. Chem. Lett. 2012, 3, 383-386 10.1021/ml300012r
85. Tirado-Rives, J.; Jorgensen, W. L. Contribution of conformer focusing to the uncertainty in predicting free energies for protein-ligand binding J. Med. Chem. 2006, 49, 5880-5884 10.1021/jm060763i
86. Afzal, O.; Kumar, S.; Kumar, R.; Firoz, A.; Jaggi, M.; Bawa, S. Docking based virtual screening and molecular dynamics study to identify potential monoacylglycerol lipase inhibitors Bioorg. Med. Chem. Lett. 2014, 24, 3986-3996 10.1016/j.bmcl.2014.06.029
87. Vyas, V. K.; Ghate, M.; Goel, A. Pharmacophore modeling, virtual screening, docking and in silico ADMET analysis of protein kinase B (PKB beta) inhibitors J. Mol. Graphics Modell. 2013, 42, 17-25 10.1016/j.jmgm.2013.01.010
88. Xiao, J.; Zhang, S.; Luo, M.; Zou, Y.; Zhang, Y.; Lai, Y. Effective virtual screening strategy focusing on the identification of novel Brutons tyrosine kinase inhibitors J. Mol. Graphics Modell. 2015, 60, 142-154 10.1016/j.jmgm.2015.05.005
89. Wilsey, C.; Gurka, J.; Toth, D.; Franco, J. A large scale virtual screen of DprE1 Comput. Biol. Chem. 2013, 47, 121-125 10.1016/j.compbiolchem.2013.08.006
90. Messaoudi, A.; Belguith, H.; Ben Hamida, J. Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 beta-lactamase Theor. Biol. Med. Modell. 2013, 10, 22 10.1186/1742-4682-10-22
91. Nogara, P. A.; Saraiva, R.d.A.; Caeran Bueno, D.; Lissner, L. J.; Lenz Dalla Corte, C.; Braga, M. M.; Rosemberg, D. B.; Rocha, J. B. Virtual screening of acetylcholinesterase inhibitors using the Lipinskis rule of five and ZINC databank BioMed Res. Int. 2015, 2015, 870389 10.1155/2015/870389
92. Regon, P.; Gogoi, D.; Rai, A. K.; Bordoloi, M.; Bezbaruah, R. L. Design of inhibitors of the HIV-1 integrase core domain using virtual screening Bioinformation 2014, 10, 76-80 10.6026/97320630010076
93. Saraswat, D.; Nehra, S.; Chaudhary, K. K.; Prasad, C. V. In-silico screening and in-vitro validation of vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors Bioinformation 2014, 10, 273-280 10.6026/97320630010273
94. Giri, P.; Kumar, A.; Taj, G. In silico-prediction of downstream MYB interacting partners of MAPK3 in Arabidopsis Bioinformation 2014, 10, 721-725 10.6026/97320630010721
95. Alhazmi, M. I. Molecular docking of selected phytocompounds with H1N1 Proteins Bioinformation 2015, 11, 196-202 10.6026/97320630011196
96. Shao, S.; Yu, R.; Yu, Y.; Li, Y. Dual-inhibitors of STAT5 and STAT3: studies from molecular docking and molecular dynamics simulations J. Mol. Model. 2014, 20, 2399 10.1007/s00894-014-2399-x
97. Sun, R.; Li, X.; Li, Y.; Zhang, X.; Li, X.; Li, X.; Shi, Z.; Bao, J. Screening of novel inhibitors targeting lactate dehydrogenase A via four molecular docking strategies and dynamics simulations J. Mol. Model. 2015, 21, 133 10.1007/s00894-015-2675-4
98. Sgrignani, J.; Novati, B.; Colombo, G.; Grazioso, G. Covalent docking of selected boron-based serine beta-lactamase inhibitors J. Comput.-Aided Mol. Des. 2015, 29, 441-450 10.1007/s10822-015-9834-7
99. Ogrizek, M.; Turk, S.; Lesnik, S.; Sosic, I.; Hodoscek, M.; Mirkovic, B.; Kos, J.; Janezic, D.; Gobec, S.; Konc, J. Molecular dynamics to enhance structure-based virtual screening on cathepsin B J. Comput.-Aided Mol. Des. 2015, 29, 707-712 10.1007/s10822-015-9847-2
100. Singh, R.; Pandey, P. N. Molecular docking and molecular dynamics study on SmHDAC1 to identify potential lead compounds against Schistosomiasis Mol. Biol. Rep. 2015, 42, 689-698 10.1007/s11033-014-3816-z
101. Pinheiro, A. S.; Duarte, J. B.; Alves, C. N.; de Molfetta, F. A. Virtual screening and molecular dynamics simulations from a bank of molecules of the Amazon region against functional NS3-4A protease-helicase enzyme of hepatitis C virus Appl. Biochem. Biotechnol. 2015, 176, 1709-1721 10.1007/s12010-015-1672-5
102. Wang, P.; Yang, F.; Yang, H.; Xu, X.; Liu, D.; Xue, W.; Zhu, F. Identification of dual active agents targeting 5-HT1A and SERT by combinatorial virtual screening methods Bio-Med. Mater. Eng. 2015, 26 (Suppl. 1) 2233-2239 10.3233/BME-151529
103. Dhanjal, J. K.; Sreenidhi, A. K.; Bafna, K.; Katiyar, S. P.; Goyal, S.; Grover, A.; Sundar, D. Computational structure-based de novo design of hypothetical inhibitors against the anti- inflammatory target COX-2 PLoS One 2015, 10, e0134691 10.1371/journal.pone.0134691
104. He, J. Y.; Li, C.; Wu, G. Discovery of potential drugs for human-infecting H7N9 virus containing R294K mutation Drug Des., Dev. Ther. 2014, 8, 2377-2390 10.2147/DDDT.S74061
105. Balakrishnan, N.; Raj, J. S.; Kandakatla, N. Discovery of novel GSK-3beta inhibitors using pharmacophore and virtual screening studies. Interdiscip. Sci.: Comput. Life Sci. 2015, DOI: 10.1007/s12539-015-0100-4.
106. Thai, K. M.; Ngo, T. D.; Phan, T. V.; Tran, T. D.; Nguyen, N. V.; Nguyen, T. H.; Le, M. T. Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products Med. Chem. 2015, 11, 135-155 10.2174/1573406410666140902110903
107. Tran, N.; Van, T.; Nguyen, H.; Le, L. Identification of novel compounds against an R294K substitution of influenza A (H7N9) virus using ensemble based drug virtual screening Int. J. Med. Sci. 2015, 12, 163-176 10.7150/ijms.10826
108. Gupta, C. L.; Akhtar, S.; Kumar, N.; Ali, J.; Pathak, N.; Bajpai, P. In silico elucidation and inhibition studies of selected phytoligands against mitogen-activated protein kinases of protozoan parasites. Interdiscip. Sci.: Comput. Life Sci. 2015, DOI: 10.1007/s12539-015-0269-6.
109. Mitra, J.; Narad, P.; Sengupta, A.; Sharma, P. D.; Paul, P. K. In silico identification of ergosterol as a novel fungal metabolite enhancing RuBisCO activity in Lycopersicum esculentum. Interdiscip. Sci.: Comput. Life Sci. 2015, DOI: 10.1007/s12539-015-0105-z.
110. Sbongile, M.; Soliman, M. E. In silico identification of irreversible cathepsin B inhibitors as anti- cancer agents: virtual screening, covalent docking analysis and molecular dynamics simulations Comb. Chem. High Throughput Screening 2015, 18, 399-410 10.2174/1386207318666150305154621
111. Batool, S.; Khan, Z. A.; Kamal, W.; Mushtaq, G.; Kamal, M. A. In silico screening for identification of novel anti-malarial inhibitors by molecular docking, pharmacophore modeling and virtual screening Med. Chem. 2015, 11, 687-700 10.2174/1573406411666150305113533
112. Kumar, H.; Raj, U.; Gupta, S.; Varadwaj, P. K. In-silico identification of inhibitors against mutated BCR-ABL protein of chronic myeloid leukemia: a virtual screening and molecular dynamics simulation study J. Biomol. Struct. Dyn. 2015, 1-13 10.1080/07391102.2015.1110046
113. Shafique, S.; Bibi, N.; Rashid, S. In silico identification of putative bifunctional Plk1 inhibitors by integrative virtual screening and structural dynamics approach J. Theor. Biol. 2016, 388, 72-84 10.1016/j.jtbi.2015.10.006
114. Pei, F.; Jin, H.; Zhou, X.; Xia, J.; Sun, L.; Liu, Z.; Zhang, L. Enrichment assessment of multiple virtual screening strategies for Toll-Like Receptor 8 agonists based on a maximal unbiased benchmarking data set Chem. Biol. Drug Des. 2015, 86, 1226-1241 10.1111/cbdd.12590
115. Kumar, R.; Chauhan, J. S.; Raghava, G. P. In silico designing and screening of antagonists against cancer drug target XIAP Curr. Cancer Drug Targets 2015, 15, 836-846 10.2174/1568009615666150706103537
116. Mathew, S.; Fatima, K.; Fatmi, M. Q.; Archunan, G.; Ilyas, M.; Begum, N.; Azhar, E.; Damanhouri, G.; Qadri, I. Computational docking study of p7 ion channel from HCV genotype 3 and genotype 4 and its interaction with natural compounds PLoS One 2015, 10, e0126510 10.1371/journal.pone.0126510
117. Lee, T. V.; Johnson, R. D.; Arcus, V. L.; Lott, J. S. Prediction of the substrate for nonribosomal peptide synthetase (NRPS) adenylation domains by virtual screening Proteins: Struct., Funct., Genet. 2015, 83, 2052-2066 10.1002/prot.24922
118. Xiang, Y.; Song, J.; Zhang, Z. Topomer CoMFA and virtual screening studies of azaindole class renin inhibitors Comb. Chem. High Throughput Screening 2014, 17, 458-472 10.2174/1386207317666140107094708
119. Arrowsmith, C. H.; Audia, J. E.; Austin, C.; Baell, J.; Bennett, J.; Blagg, J.; Bountra, C.; Brennan, P. E.; Brown, P. J.; Bunnage, M. E.; Buser-Doepner, C.; Campbell, R. M.; Carter, A. J.; Cohen, P.; Copeland, R. A.; Cravatt, B.; Dahlin, J. L.; Dhanak, D.; Edwards, A. M.; Frederiksen, M.; Frye, S. V.; Gray, N.; Grimshaw, C. E.; Hepworth, D.; Howe, T.; Huber, K. V.; Jin, J.; Knapp, S.; Kotz, J. D.; Kruger, R. G.; Lowe, D.; Mader, M. M.; Marsden, B.; Mueller-Fahrnow, A.; Muller, S.; OHagan, R. C.; Overington, J. P.; Owen, D. R.; Rosenberg, S. H.; Roth, B.; Ross, R.; Schapira, M.; Schreiber, S. L.; Shoichet, B.; Sundstrom, M.; Superti-Furga, G.; Taunton, J.; Toledo-Sherman, L.; Walpole, C.; Walters, M. A.; Willson, T. M.; Workman, P.; Young, R. N.; Zuercher, W. J. The promise and peril of chemical probes Nat. Chem. Biol. 2015, 11, 536-541 10.1038/nchembio.1867
120. Baell, J. B.; Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays J. Med. Chem. 2010, 53, 2719-2740 10.1021/jm901137j
121. Shoichet, B. K. Screening in a spirit haunted world Drug Discovery Today 2006, 11, 607-615 10.1016/j.drudis.2006.05.014
122. Walters, W. P.; Namchuk, M. Designing screens: how to make your hits a hit Nat. Rev. Drug Discovery 2003, 2, 259-266 10.1038/nrd1063
123. Rishton, G. M. Nonleadlikeness and leadlikeness in biochemical screening Drug Discovery Today 2003, 8, 86-96 10.1016/S1359644602025722
124. Simeonov, A.; Jadhav, A.; Thomas, C. J.; Wang, Y.; Huang, R.; Southall, N. T.; Shinn, P.; Smith, J.; Austin, C. P.; Auld, D. S.; Inglese, J. Fluorescence spectroscopic profiling of compound libraries J. Med. Chem. 2008, 51, 2363-2371 10.1021/jm701301m
125. Lea, W. A.; Simeonov, A. Fluorescence polarization assays in small molecule screening Expert Opin. Drug Discovery 2011, 6, 17-32 10.1517/17460441.2011.537322
126. Thorne, N.; Auld, D. S.; Inglese, J. Apparent activity in high-throughput screening: origins of compound-dependent assay interference Curr. Opin. Chem. Biol. 2010, 14, 315-324 10.1016/j.cbpa.2010.03.020
127. McGovern, S. L.; Caselli, E.; Grigorieff, N.; Shoichet, B. K. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening J. Med. Chem. 2002, 45, 1712-1722 10.1021/jm010533y
128. Feng, B. Y.; Shelat, A.; Doman, T. N.; Guy, R. K.; Shoichet, B. K. High-throughput assays for promiscuous inhibitors Nat. Chem. Biol. 2005, 1, 146-148 10.1038/nchembio718
129. Coan, K. E.; Shoichet, B. K. Stoichiometry and physical chemistry of promiscuous aggregate-based inhibitors J. Am. Chem. Soc. 2008, 130, 9606-9612 10.1021/ja802977h
130. Park, H.; Yu, K. R.; Ku, B.; Kim, B. Y.; Kim, S. J. Identification of novel PTPRQ phosphatase inhibitors based on the virtual screening with docking simulations Theor. Biol. Med. Modell. 2013, 10, 49 10.1186/1742-4682-10-49
131. Hou, X.; Li, K.; Yu, X.; Sun, J. P.; Fang, H. Protein flexibility in docking-based virtual screening: discovery of novel lymphoid-specific tyrosine phosphatase inhibitors using multiple crystal structures J. Chem. Inf. Model. 2015, 55, 1973-1983 10.1021/acs.jcim.5b00344
132. 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. Graphics Modell. 2015, 60, 124-131 10.1016/j.jmgm.2015.05.001
133. Park, H.; Kim, S. Y.; Kyung, A.; Yoon, T. S.; Ryu, S. E.; Jeong, D. G. Structure-based virtual screening approach to the discovery of novel PTPMT1 phosphatase inhibitors Bioorg. Med. Chem. Lett. 2012, 22, 1271-1275 10.1016/j.bmcl.2011.10.083
134. Wolan, D. W.; Zorn, J. A.; Gray, D. C.; Wells, J. A. Small-molecule activators of a proenzyme Science 2009, 326, 853-858 10.1126/science.1177585
135. Allen, W. J.; Yi, H. A.; Gochin, M.; Jacobs, A.; Rizzo, R. C. Small molecule inhibitors of HIVgp41 N-heptad repeat trimer formation Bioorg. Med. Chem. Lett. 2015, 25, 2853-2859 10.1016/j.bmcl.2015.04.067
136. Dong, X.; Zhou, X.; Jing, H.; Chen, J.; Liu, T.; Yang, B.; He, Q.; Hu, Y. Pharmacophore identification, virtual screening and biological evaluation of prenylated flavonoids derivatives as PKB/Akt1 inhibitors Eur. J. Med. Chem. 2011, 46, 5949-5958 10.1016/j.ejmech.2011.10.006
137. Zhong, Z.; Liu, L. J.; Dong, Z. Q.; Lu, L.; Wang, M.; Leung, C. H.; Ma, D. L.; Wang, Y. Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database Chem. Commun. (Cambridge, U. K.) 2015, 51, 11178-11181 10.1039/C5CC02728D
138. Mohammed, A.; Al-Numair, K. S.; Balakrishnan, A. Docking studies on the interaction of flavonoids with fat mass and obesity associated protein Pak. J. Pharm. Sci. 2015, 28, 1647-1653
139. Brecher, M.; Chen, H.; Liu, B.; Banavali, N. K.; Jones, S. A.; Zhang, J.; Li, Z.; Kramer, L. D.; Li, H. Novel broad spectrum inhibitors targeting the flavivirus methyltransferase PLoS One 2015, 10, e0130062 10.1371/journal.pone.0130062
140. Walters, W.; Namchuk, M. Designing screens: how to make your hits a hit Nat. Rev. Drug Discovery 2003, 2, 259-266 10.1038/nrd1063
141. Thorne, N.; Shen, M.; Lea, W. A.; Simeonov, A.; Lovell, S.; Auld, D. S.; Inglese, J. Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter Chem. Biol. 2012, 19, 1060-1072 10.1016/j.chembiol.2012.07.015
142. Feng, B. Y.; Shoichet, B. K. A detergent-based assay for the detection of promiscuous inhibitors Nat. Protoc. 2006, 1, 550-553 10.1038/nprot.2006.77
143. Sassano, M. F.; Doak, A. K.; Roth, B. L.; Shoichet, B. K. Colloidal aggregation causes inhibition of G protein-coupled receptors J. Med. Chem. 2013, 56, 2406-2414 10.1021/jm301749y
144. Owen, S. C.; Doak, A. K.; Wassam, P.; Shoichet, M. S.; Shoichet, B. K. Colloidal aggregation affects the efficacy of anticancer drugs in cell culture ACS Chem. Biol. 2012, 7, 1429-1435 10.1021/cb300189b
145. Shoichet, B. K. Interpreting steep dose-response curves in early inhibitor discovery J. Med. Chem. 2006, 49, 7274-7277 10.1021/jm061103g
146. Fukunishi, Y.; Nakamura, H. Improved estimation of protein-ligand binding free energy by using the ligand-entropy and mobility of water molecules Pharmaceuticals 2013, 6, 604-622 10.3390/ph6050604
147. Barillari, C.; Taylor, J.; Viner, R.; Essex, J. W. Classification of water molecules in protein binding sites J. Am. Chem. Soc. 2007, 129, 2577-2587 10.1021/ja066980q
148. Michel, J.; Tirado-Rives, J.; Jorgensen, W. L. Prediction of the water content in protein binding sites J. Phys. Chem. B 2009, 113, 13337-13346 10.1021/jp9047456
149. Abel, R.; Salam, N. K.; Shelley, J.; Farid, R.; Friesner, R. A.; Sherman, W. Contribution of explicit solvent effects to the binding affinity of small-molecule inhibitors in blood coagulation factor serine proteases ChemMedChem 2011, 6, 1049-1066 10.1002/cmdc.201000533
150. Zheng, M.; Li, Y.; Xiong, B.; Jiang, H.; Shen, J. Water PMF for predicting the properties of water molecules in protein binding site J. Comput. Chem. 2013, 34, 583-592 10.1002/jcc.23170
151. Forli, S.; Olson, A. J. A force field with discrete displaceable waters and desolvation entropy for hydrated ligand docking J. Med. Chem. 2012, 55, 623-638 10.1021/jm2005145
152. Pottel, J.; Therrien, E.; Gleason, J. L.; Moitessier, N. Docking ligands into flexible and solvated macromolecules. 6. Development and application to the docking of HDACs and other zinc metalloenzymes inhibitors J. Chem. Inf. Model. 2014, 54, 254-265 10.1021/ci400550m
153. Adeniyi, A. A.; Ajibade, P. A. Comparing the suitability of autodock, gold and glide for the docking and predicting the possible targets of Ru(II)-based complexes as anticancer agents Molecules 2013, 18, 3760-3778 10.3390/molecules18043760
154. Li, X.; Jacobson, M. P.; Zhu, K.; Zhao, S.; Friesner, R. A. Assignment of polar states for protein amino acid residues using an interaction cluster decomposition algorithm and its application to high resolution protein structure modeling Proteins: Struct., Funct., Genet. 2007, 66, 824-837 10.1002/prot.21125
155. Kruger, J.; Grunzke, R.; Herres-Pawlis, S.; Hoffmann, A.; de la Garza, L.; Kohlbacher, O.; Nagel, W. E.; Gesing, S. Performance studies on distributed virtual screening BioMed Res. Int. 2014, 2014, 624024 10.1155/2014/624024
156. Trott, O.; Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading J. Comput. Chem. 2010, 31, 455-461 10.1002/jcc.21334
157. Kasam, V.; Salzemann, J.; Botha, M.; Dacosta, A.; Degliesposti, G.; Isea, R.; Kim, D.; Maass, A.; Kenyon, C.; Rastelli, G.; Hofmann-Apitius, M.; Breton, V. WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures Malar. J. 2009, 8, 88 10.1186/1475-2875-8-88
158. CombiGlide; Schrodinger: New York, 2015.
159. Lazaridis, T. Inhomogeneous fluid approach to solvation thermodynamics. 2. Applications to simple fluids J. Phys. Chem. B 1998, 102, 3542-3550 10.1021/jp972358w
160. Repasky, M. P.; Murphy, R. B.; Banks, J. L.; Greenwood, J. R.; Tubert-Brohman, I.; Bhat, S.; Friesner, R. A. Docking performance of the glide program as evaluated on the Astex and DUD datasets: a complete set of glide SP results and selected results for a new scoring function integrating WaterMap and glide J. Comput.-Aided Mol. Des. 2012, 26, 787-799 10.1007/s10822-012-9575-9
161. Nguyen, C. N.; Young, T. K.; Gilson, M. K. Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril J. Chem. Phys. 2012, 137, 044101 10.1063/1.4733951
162. Irwin, J. J.; Shoichet, B. K. ZINC - A free database of commercially available compounds for virtual screening J. Chem. Inf. Model. 2005, 45, 177-182 10.1021/ci049714+
163. Sterling, T.; Irwin, J. J. ZINC 15-Ligand discovery for everyone J. Chem. Inf. Model. 2015, 55, 2324-2337 10.1021/acs.jcim.5b00559
164. ten Brink, T.; Exner, T. E. pK(a) based protonation states and microspecies for protein-ligand docking J. Comput.-Aided Mol. Des. 2010, 24, 935-942 10.1007/s10822-010-9385-x
165. Kim, M. O.; McCammon, J. A. Computation of pH-dependent binding free energies Biopolymers 2016, 105, 43-49 10.1002/bip.22702
166. Hawkins, P. C.; Nicholls, A. Conformer generation with OMEGA: learning from the data set and the analysis of failures J. Chem. Inf. Model. 2012, 52, 2919-2936 10.1021/ci300314k
167. Jorgensen, W. L.; Thomas, L. L. Perspective on free-energy perturbation calculations for chemical equilibria J. Chem. Theory Comput. 2008, 4, 869-876 10.1021/ct800011m
168. Mobley, D. L.; Dill, K. A. Binding of small-molecule ligands to proteins: "what you see" is not always "what you get" Structure 2009, 17, 489-498 10.1016/j.str.2009.02.010
169. Mobley, D. L.; Graves, A. P.; Chodera, J. D.; McReynolds, A. C.; Shoichet, B. K.; Dill, K. A. Predicting absolute ligand binding free energies to a simple model site J. Mol. Biol. 2007, 371, 1118-1134 10.1016/j.jmb.2007.06.002
170. Rocklin, G. J.; Boyce, S. E.; Fischer, M.; Fish, I.; Mobley, D. L.; Shoichet, B. K.; Dill, K. A. Blind prediction of charged ligand binding affinities in a model binding site J. Mol. Biol. 2013, 425, 4569-4583 10.1016/j.jmb.2013.07.030
171. Lippert, R. A.; Predescu, C.; Ierardi, D. J.; Mackenzie, K. M.; Eastwood, M. P.; Dror, R. O.; Shaw, D. E. Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure J. Chem. Phys. 2013, 139, 164106 10.1063/1.4825247
172. Dror, R. O.; Green, H. F.; Valant, C.; Borhani, D. W.; Valcourt, J. R.; Pan, A. C.; Arlow, D. H.; Canals, M.; Lane, J. R.; Rahmani, R.; Baell, J. B.; Sexton, P. M.; Christopoulos, A.; Shaw, D. E. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs Nature 2013, 503, 295-299 10.1038/nature12595
173. Shukla, D.; Hernandez, C. X.; Weber, J. K.; Pande, V. S. Markov state models provide insights into dynamic modulation of protein function Acc. Chem. Res. 2015, 48, 414-422 10.1021/ar5002999
174. Barelier, S.; Eidam, O.; Fish, I.; Hollander, J.; Figaroa, F.; Nachane, R.; Irwin, J. J.; Shoichet, B. K.; Siegal, G. Increasing chemical space coverage by combining empirical and computational fragment screens ACS Chem. Biol. 2014, 9, 1528-1535 10.1021/cb5001636
175. London, N.; Miller, R. M.; Krishnan, S.; Uchida, K.; Irwin, J. J.; Eidam, O.; Gibold, L.; Cimermancic, P.; Bonnet, R.; Shoichet, B. K.; Taunton, J. Covalent docking of large libraries for the discovery of chemical probes Nat. Chem. Biol. 2014, 10, 1066-1072 10.1038/nchembio.1666
176. Bianco, G.; Forli, S.; Goodsell, D. S.; Olson, A. J. Covalent docking using autodock: Two-point attractor and flexible side chain methods Protein Sci. 2016, 25, 295-301 10.1002/pro.2733
177. Zhu, K.; Borrelli, K. W.; Greenwood, J. R.; Day, T.; Abel, R.; Farid, R. S.; Harder, E. Docking covalent inhibitors: a parameter free approach to pose prediction and scoring J. Chem. Inf. Model. 2014, 54, 1932-1940 10.1021/ci500118s
178. Ouyang, X.; Zhou, S.; Ge, Z.; Li, R.; Kwoh, C. K. CovalentDock Cloud: a web server for automated covalent docking Nucleic Acids Res. 2013, 41, W329-332 10.1093/nar/gkt406
179. Ouyang, X.; Zhou, S.; Su, C. T.; Ge, Z.; Li, R.; Kwoh, C. K. CovalentDock: automated covalent docking with parameterized covalent linkage energy estimation and molecular geometry constraints J. Comput. Chem. 2013, 34, 326-336 10.1002/jcc.23136
180. Toledo Warshaviak, D.; Golan, G.; Borrelli, K. W.; Zhu, K.; Kalid, O. Structure-based virtual screening approach for discovery of covalently bound ligands J. Chem. Inf. Model. 2014, 54, 1941-1950 10.1021/ci500175r
181. Munoz, M.; Sospedra, P.; Gomara, M. J.; Mestres, C.; Haro, I. The covalent coupling of HAV-VP3 (110-121) synthetic peptide to liposomes: physicochemical studies Int. J. Pharm. 2004, 269, 177-184 10.1016/j.ijpharm.2003.09.014
182. Scholz, C.; Knorr, S.; Hamacher, K.; Schmidt, B. DOCKTITE-a highly versatile step-by-step workflow for covalent docking and virtual screening in the molecular operating environment J. Chem. Inf. Model. 2015, 55, 398-406 10.1021/ci500681r
183. Schmidt, T. C.; Welker, A.; Rieger, M.; Sahu, P. K.; Sotriffer, C. A.; Schirmeister, T.; Engels, B. Protocol for rational design of covalently interacting inhibitors ChemPhysChem 2014, 15, 3226-3235 10.1002/cphc.201402542
184. Dong, G. Q.; Calhoun, S.; Fan, H.; Kalyanaraman, C.; Branch, M. C.; Mashiyama, S. T.; London, N.; Jacobson, M. P.; Babbitt, P. C.; Shoichet, B. K.; Armstrong, R. N.; Sali, A. Prediction of substrates for glutathione transferases by covalent docking J. Chem. Inf. Model. 2014, 54, 1687-1699 10.1021/ci5001554
185. Zhang, S.; Tan, J.; Lai, Z.; Li, Y.; Pang, J.; Xiao, J.; Huang, Z.; Zhang, Y.; Ji, H.; Lai, Y. Effective virtual screening strategy toward covalent ligands: identification of novel NEDD8-activating enzyme inhibitors J. Chem. Inf. Model. 2014, 54, 1785-1797 10.1021/ci5002058
186. Fakhouri, L.; El-Elimat, T.; Hurst, D. P.; Reggio, P. H.; Pearce, C. J.; Oberlies, N. H.; Croatt, M. P. Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues Bioorg. Med. Chem. 2015, 23, 6993-6999 10.1016/j.bmc.2015.09.037
187. Li, A.; Sun, H.; Du, L.; Wu, X.; Cao, J.; You, Q.; Li, Y. Discovery of novel covalent proteasome inhibitors through a combination of pharmacophore screening, covalent docking, and molecular dynamics simulations J. Mol. Model. 2014, 20, 2515 10.1007/s00894-014-2515-y
188. London, N.; Farelli, J. D.; Brown, S. D.; Liu, C.; Huang, H.; Korczynska, M.; Al-Obaidi, N. F.; Babbitt, P. C.; Almo, S. C.; Allen, K. N.; Shoichet, B. K. Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases Biochemistry 2015, 54, 528-537 10.1021/bi501140k
189. Webb, B.; Lasker, K.; Schneidman-Duhovny, D.; Tjioe, E.; Phillips, J.; Kim, S. J.; Velazquez-Muriel, J.; Russel, D.; Sali, A. Modeling of proteins and their assemblies with the integrative modeling platform Methods Mol. Biol. (N. Y., NY, U. S.) 2011, 781, 377-397 10.1007/978-1-61779-276-2-19
190. Evers, A.; Klebe, G. Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model J. Med. Chem. 2004, 47, 5381-5392 10.1021/jm0311487
191. Evers, A.; Klebe, G. Ligand-supported homology modeling of g-protein-coupled receptor sites: models sufficient for successful virtual screening Angew. Chem., Int. Ed. 2004, 43, 248-251 10.1002/anie.200352776
192. Zhao, S.; Kumar, R.; Sakai, A.; Vetting, M. W.; Wood, B. M.; Brown, S.; Bonanno, J. B.; Hillerich, B. S.; Seidel, R. D.; Babbitt, P. C.; Almo, S. C.; Sweedler, J. V.; Gerlt, J. A.; Cronan, J. E.; Jacobson, M. P. Discovery of new enzymes and metabolic pathways by using structure and genome context Nature 2013, 502, 698-702 10.1038/nature12576
193. Kalyanaraman, C.; Imker, H. J.; Fedorov, A. A.; Fedorov, E. V.; Glasner, M. E.; Babbitt, P. C.; Almo, S. C.; Gerlt, J. A.; Jacobson, M. P. Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening Structure 2008, 16, 1668-1677 10.1016/j.str.2008.08.015
194. Fan, H.; Hitchcock, D. S.; Seidel, R. D., 2nd; Hillerich, B.; Lin, H.; Almo, S. C.; Sali, A.; Shoichet, B. K.; Raushel, F. M. Assignment of pterin deaminase activity to an enzyme of unknown function guided by homology modeling and docking J. Am. Chem. Soc. 2013, 135, 795-803 10.1021/ja309680b
195. Jensen, C.; Herold, P.; Brunner, H. R. Aliskiren: the first renin inhibitor for clinical treatment Nat. Rev. Drug Discovery 2008, 7, 399-410 10.1038/nrd2550
196. Barelier, S.; Sterling, T.; OMeara, M. J.; Shoichet, B. K. The recognition of identical ligands by unrelated proteins ACS Chem. Biol. 2015, 10, 2772-2784 10.1021/acschembio.5b00683
197. Tondi, D.; Morandi, F.; Bonnet, R.; Costi, M. P.; Shoichet, B. K. Structure-based optimization of a non-beta-lactam lead results in inhibitors that do not up-regulate beta-lactamase expression in cell culture J. Am. Chem. Soc. 2005, 127, 4632-4639 10.1021/ja042984o
198. Hermann, J. C.; Marti-Arbona, R.; Fedorov, A. A.; Fedorov, E.; Almo, S. C.; Shoichet, B. K.; Raushel, F. M. Structure-based activity prediction for an enzyme of unknown function Nature 2007, 448, 775-779 10.1038/nature05981
199. Sali, D.; Bycroft, M.; Fersht, A. R. Stabilization of protein structure by interaction of alpha-helix dipole with a charged side chain Nature 1988, 335, 740-743 10.1038/335740a0
200. Eswar, N.; Sali, A. Comparative modeling of drug target proteins. In Comprehensive Medicinal Chemistry II; Taylor, J. B.; Triggle, D. J., Eds.; Elsevier, 2007; Vol. 4, pp 216-231.
201. Zhou, Y.; Ma, J.; Lin, X.; Huang, X. P.; Wu, K.; Huang, N. Structure-based discovery of novel and selective 5-hydroxytryptamine 2B receptor antagonists for the treatment of irritable bowel syndrome J. Med. Chem. 2016, 59, 707-720 10.1021/acs.jmedchem.5b01631
202. Yan, C.; Liu, D.; Li, L.; Wempe, M. F.; Guin, S.; Khanna, M.; Meier, J.; Hoffman, B.; Owens, C.; Wysoczynski, C. L.; Nitz, M. D.; Knabe, W. E.; Ahmed, M.; Brautigan, D. L.; Paschal, B. M.; Schwartz, M. A.; Jones, D. N.; Ross, D.; Meroueh, S. O.; Theodorescu, D. Discovery and characterization of small molecules that target the GTPase Ral Nature 2014, 515, 443-447 10.1038/nature13713
203. Gruneberg, S.; Wendt, B.; Klebe, G. Subnanomolar inhibitors from computer screening: a model study using human carbonic anhydrase II Angew. Chem., Int. Ed. 2001, 40, 389-393 10.1002/1521-3773(20010119)40:2<389::AID-ANIE389>3.0.CO;2-#
204. de Graaf, C.; Kooistra, A. J.; Vischer, H. F.; Katritch, V.; Kuijer, M.; Shiroishi, M.; Iwata, S.; Shimamura, T.; Stevens, R. C.; de Esch, I. J.; Leurs, R. Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor J. Med. Chem. 2011, 54, 8195-8206 10.1021/jm2011589
205. Kolb, P.; Rosenbaum, D. M.; Irwin, J. J.; Fung, J. J.; Kobilka, B. K.; Shoichet, B. K. Structure-based discovery of beta2-adrenergic receptor ligands Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 6843-6848 10.1073/pnas.0812657106
206. Rodriguez, D.; Gao, Z. G.; Moss, S. M.; Jacobson, K. A.; Carlsson, J. Molecular docking screening using agonist-bound GPCR structures: probing the A2A adenosine receptor J. Chem. Inf. Model. 2015, 55, 550-563 10.1021/ci500639g
207. Colas, C.; Grewer, C.; Otte, N. J.; Gameiro, A.; Albers, T.; Singh, K.; Shere, H.; Bonomi, M.; Holst, J.; Schlessinger, A. Ligand discovery for the alanine-serine-cysteine transporter (ASCT2, SLC1A5) from homology modeling and virtual screening PLoS Comput. Biol. 2015, 11, e1004477 10.1371/journal.pcbi.1004477
208. Katritch, V.; Jaakola, V. P.; Lane, J. R.; Lin, J.; Ijzerman, A. P.; Yeager, M.; Kufareva, I.; Stevens, R. C.; Abagyan, R. Structure-based discovery of novel chemotypes for adenosine A(2A) receptor antagonists J. Med. Chem. 2010, 53, 1799-1809 10.1021/jm901647p
209. Carlsson, J.; Yoo, L.; Gao, Z. G.; Irwin, J. J.; Shoichet, B. K.; Jacobson, K. A. Structure-based discovery of A2A adenosine receptor ligands J. Med. Chem. 2010, 53, 3748-3755 10.1021/jm100240h
210. Park, H.; Chien, P. N.; Ryu, S. E. Discovery of potent inhibitors of receptor protein tyrosine phosphatase sigma through the structure-based virtual screening Bioorg. Med. Chem. Lett. 2012, 22, 6333-6337 10.1016/j.bmcl.2012.08.081
211. Zarzycka, B.; Seijkens, T.; Nabuurs, S. B.; Ritschel, T.; Grommes, J.; Soehnlein, O.; Schrijver, R.; van Tiel, C. M.; Hackeng, T. M.; Weber, C.; Giehler, F.; Kieser, A.; Lutgens, E.; Vriend, G.; Nicolaes, G. A. Discovery of small molecule CD40-TRAF6 inhibitors J. Chem. Inf. Model. 2015, 55, 294-307 10.1021/ci500631e
212. Fazi, R.; Tintori, C.; Brai, A.; Botta, L.; Selvaraj, M.; Garbelli, A.; Maga, G.; Botta, M. Homology Model-Based Virtual Screening for the Identification of Human Helicase DDX3 Inhibitors J. Chem. Inf. Model. 2015, 55, 2443-2454 10.1021/acs.jcim.5b00419
213. Carlsson, J.; Coleman, R. G.; Setola, V.; Irwin, J. J.; Fan, H.; Schlessinger, A.; Sali, A.; Roth, B. L.; Shoichet, B. K. Ligand discovery from a dopamine D3 receptor homology model and crystal structure Nat. Chem. Biol. 2011, 7, 769-778 10.1038/nchembio.662
214. Sorna, V.; Theisen, E. R.; Stephens, B.; Warner, S. L.; Bearss, D. J.; Vankayalapati, H.; Sharma, S. High-throughput virtual screening identifies novel N′-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors J. Med. Chem. 2013, 56, 9496-9508 10.1021/jm400870h
215. Mahasenan, K. V.; Li, C. Novel inhibitor discovery through virtual screening against multiple protein conformations generated via ligand-directed modeling: a maternal embryonic leucine zipper kinase example J. Chem. Inf. Model. 2012, 52, 1345-1355 10.1021/ci300040c
216. Nolan, K. A.; Dunstan, M. S.; Caraher, M. C.; Scott, K. A.; Leys, D.; Stratford, I. J. In silico screening reveals structurally diverse, nanomolar inhibitors of NQO2 that are functionally active in cells and can modulate NF-kappaB signaling Mol. Cancer Ther. 2012, 11, 194-203 10.1158/1535-7163.MCT-11-0543
217. Borriello, L.; Montes, M.; Lepelletier, Y.; Leforban, B.; Liu, W. Q.; Demange, L.; Delhomme, B.; Pavoni, S.; Jarray, R.; Boucher, J. L.; Dufour, S.; Hermine, O.; Garbay, C.; Hadj-Slimane, R.; Raynaud, F. Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model Cancer Lett. (N. Y., NY, U. S.) 2014, 349, 120-127 10.1016/j.canlet.2014.04.004
218. Choi, H.; Park, H. J.; Shin, J. C.; Ko, H. S.; Lee, J. K.; Lee, S.; Park, H.; Hong, S. Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors Bioorg. Med. Chem. Lett. 2012, 22, 2195-2199 10.1016/j.bmcl.2012.01.104
219. Pala, N.; Stevaert, A.; Dallocchio, R.; Dessi, A.; Rogolino, D.; Carcelli, M.; Sanna, V.; Sechi, M.; Naesens, L. Virtual screening and biological validation of novel influenza virus PA endonuclease Inhibitors ACS Med. Chem. Lett. 2015, 6, 866-871 10.1021/acsmedchemlett.5b00109
220. Di Leva, F. S.; Zizza, P.; Cingolani, C.; DAngelo, C.; Pagano, B.; Amato, J.; Salvati, E.; Sissi, C.; Pinato, O.; Marinelli, L.; Cavalli, A.; Cosconati, S.; Novellino, E.; Randazzo, A.; Biroccio, A. Exploring the chemical space of G-quadruplex binders: discovery of a novel chemotype targeting the human telomeric sequence J. Med. Chem. 2013, 56, 9646-9654 10.1021/jm401185b
221. Wang, D.; Wang, F.; Tan, Y.; Dong, L.; Chen, L.; Zhu, W.; Wang, H. Discovery of potent small molecule inhibitors of DYRK1A by structure-based virtual screening and bioassay Bioorg. Med. Chem. Lett. 2012, 22, 168-171 10.1016/j.bmcl.2011.11.043
222. de Graaf, C.; Rein, C.; Piwnica, D.; Giordanetto, F.; Rognan, D. Structure-based discovery of allosteric modulators of two related class B G-protein-coupled receptors ChemMedChem 2011, 6, 2159-2169 10.1002/cmdc.201100317
223. Kalid, O.; Toledo Warshaviak, D.; Shechter, S.; Sherman, W.; Shacham, S. Consensus Induced Fit Docking (cIFD): methodology, validation, and application to the discovery of novel Crm1 inhibitors J. Comput.-Aided Mol. Des. 2012, 26, 1217-1228 10.1007/s10822-012-9611-9
224. Chang, C. K.; Jeyachandran, S.; Hu, N. J.; Liu, C. L.; Lin, S. Y.; Wang, Y. S.; Chang, Y. M.; Hou, M. H. Structure-based virtual screening and experimental validation of the discovery of inhibitors targeted towards the human coronavirus nucleocapsid protein Mol. BioSyst. 2016, 12, 59-66 10.1039/C5MB00582E
225. Cho, Y.; Ioerger, T. R.; Sacchettini, J. C. Discovery of novel nitrobenzothiazole inhibitors for Mycobacterium tuberculosis ATP phosphoribosyl transferase (HisG) through virtual screening J. Med. Chem. 2008, 51, 5984-5992 10.1021/jm800328v
226. Liu, J.; Liu, B.; Guo, G.; Jing, Y.; Zhao, G. Discovery of novel androgen receptor antagonists: a hybrid approach of pharmacophore-based and docking-based virtual screening Anti-Cancer Drugs 2015, 26, 747-753 10.1097/CAD.0000000000000245
227. Wiggers, H. J.; Rocha, J. R.; Fernandes, W. B.; Sesti-Costa, R.; Carneiro, Z. A.; Cheleski, J.; da Silva, A. B.; Juliano, L.; Cezari, M. H.; Silva, J. S.; McKerrow, J. H.; Montanari, C. A. Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay PLoS Neglected Trop. Dis. 2013, 7, e2370 10.1371/journal.pntd.0002370
228. Park, H.; Park, S. Y.; Oh, J. J.; Ryu, S. E. Identification of potent VHZ phosphatase inhibitors with structure-based virtual screening J. Biomol. Screening 2013, 18, 226-231 10.1177/1087057112463067
229. Meng, F.; Cheng, S.; Ding, H.; Liu, S.; Liu, Y.; Zhu, K.; Chen, S.; Lu, J.; Xie, Y.; Li, L.; Liu, R.; Shi, Z.; Zhou, Y.; Liu, Y. C.; Zheng, M.; Jiang, H.; Lu, W.; Liu, H.; Luo, C. Discovery and optimization of novel, selective histone methyltransferase SET7 inhibitors by pharmacophore- and docking-based virtual screening J. Med. Chem. 2015, 58, 8166-8181 10.1021/acs.jmedchem.5b01154
230. Parmenopoulou, V.; Kantsadi, A. L.; Tsirkone, V. G.; Chatzileontiadou, D. S.; Manta, S.; Zographos, S. E.; Molfeta, C.; Archontis, G.; Agius, L.; Hayes, J. M.; Leonidas, D. D.; Komiotis, D. Structure based inhibitor design targeting glycogen phosphorylase B. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-d-glucopyranosylamines Bioorg. Med. Chem. 2014, 22, 4810-4825 10.1016/j.bmc.2014.06.058
231. Li, C.; Lu, W.; Lu, C.; Xiao, W.; Shen, X.; Huang, J.; Liu, G.; Tang, Y. Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based virtual screening J. Mol. Model. 2012, 18, 4033-4042 10.1007/s00894-012-1394-3
232. Lagos, C. F.; Vecchiola, A.; Allende, F.; Fuentes, C. A.; Tichauer, J. E.; Valdivia, C.; Solari, S.; Campino, C.; Tapia-Castillo, A.; Baudrand, R.; Villarroel, P.; Cifuentes, M.; Owen, G. I.; Carvajal, C. A.; Fardella, C. E. Identification of novel 11beta-HSD1 inhibitors by combined ligand- and structure-based virtual screening Mol. Cell. Endocrinol. 2014, 384, 71-82 10.1016/j.mce.2014.01.011
233. Cancellieri, M.; Bassetto, M.; Widjaja, I.; van Kuppeveld, F.; de Haan, C. A.; Brancale, A. In silico structure-based design and synthesis of novel anti-RSV compounds Antiviral Res. 2015, 122, 46-50 10.1016/j.antiviral.2015.08.003
234. Rettenmaier, T. J.; Fan, H.; Karpiak, J.; Doak, A.; Sali, A.; Shoichet, B. K.; Wells, J. A. Small-molecule allosteric modulators of the protein kinase PDK1 from structure-based docking J. Med. Chem. 2015, 58, 8285-8291 10.1021/acs.jmedchem.5b01216
235. Gradler, U.; Gerber, H. D.; Goodenough-Lashua, D. M.; Garcia, G. A.; Ficner, R.; Reuter, K.; Stubbs, M. T.; Klebe, G. A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase J. Mol. Biol. 2001, 306, 455-467 10.1006/jmbi.2000.4256
236. Ramirez, U. D.; Nikonova, A. S.; Liu, H.; Pecherskaya, A.; Lawrence, S. H.; Serebriiskii, I. G.; Zhou, Y.; Robinson, M. K.; Einarson, M. B.; Golemis, E. A.; Jaffe, E. K. Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization BMC Cancer 2015, 15, 436 10.1186/s12885-015-1415-6
237. Gasser, A.; Brogi, S.; Urayama, K.; Nishi, T.; Kurose, H.; Tafi, A.; Ribeiro, N.; Desaubry, L.; Nebigil, C. G. Discovery and cardioprotective effects of the first non-peptide agonists of the G protein-coupled prokineticin receptor-1 PLoS One 2015, 10, e0121027 10.1371/journal.pone.0121027
238. Jang, J. W.; Cho, N. C.; Min, S. J.; Cho, Y. S.; Park, K. D.; Seo, S. H.; No, K. T.; Pae, A. N. Novel scaffold identification of mGlu1 receptor negative allosteric modulators using a hierarchical virtual screening approach Chem. Biol. Drug Des. 2016, 87, 239-256 10.1111/cbdd.12654
239. Lee, H.; Mittal, A.; Patel, K.; Gatuz, J. L.; Truong, L.; Torres, J.; Mulhearn, D. C.; Johnson, M. E. Identification of novel drug scaffolds for inhibition of SARS-CoV 3-chymotrypsin-like protease using virtual and high-throughput screenings Bioorg. Med. Chem. 2014, 22, 167-177 10.1016/j.bmc.2013.11.041
240. Duffy, B. C.; Liu, S.; Martin, G. S.; Wang, R.; Hsia, M. M.; Zhao, H.; Guo, C.; Ellis, M.; Quinn, J. F.; Kharenko, O. A.; Norek, K.; Gesner, E. M.; Young, P. R.; McLure, K. G.; Wagner, G. S.; Lakshminarasimhan, D.; White, A.; Suto, R. K.; Hansen, H. C.; Kitchen, D. B. Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design Bioorg. Med. Chem. Lett. 2015, 25, 2818-2823 10.1016/j.bmcl.2015.04.107
241. Ouizougun-Oubari, M.; Pereira, N.; Tarus, B.; Galloux, M.; Lassoued, S.; Fix, J.; Tortorici, M. A.; Hoos, S.; Baron, B.; England, P.; Desmaele, D.; Couvreur, P.; Bontems, F.; Rey, F. A.; Eleouet, J. F.; Sizun, C.; Slama-Schwok, A.; Duquerroy, S. A druggable pocket at the nucleocapsid/phosphoprotein interaction site of human respiratory syncytial virus J. Virol. 2015, 89, 11129-11143 10.1128/JVI.01612-15
242. Brenk, R.; Vetter, S. W.; Boyce, S. E.; Goodin, D. B.; Shoichet, B. K. Probing molecular docking in a charged model binding site J. Mol. Biol. 2006, 357, 1449-1470 10.1016/j.jmb.2006.01.034
243. Fischer, M.; Coleman, R. G.; Fraser, J. S.; Shoichet, B. K. Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery Nat. Chem. 2014, 6, 575-583 10.1038/nchem.1954
244. Wei, B. Q.; Baase, W. A.; Weaver, L. H.; Matthews, B. W.; Shoichet, B. K. A model binding site for testing scoring functions in molecular docking J. Mol. Biol. 2002, 322, 339-355 10.1016/S0022-2836(02)00777-5
245. Graves, A. P.; Shivakumar, D. M.; Boyce, S. E.; Jacobson, M. P.; Case, D. A.; Shoichet, B. K. Rescoring docking hit lists for model cavity sites: predictions and experimental testing J. Mol. Biol. 2008, 377, 914-934 10.1016/j.jmb.2008.01.049
246. Tanwar, O.; Tanwar, L.; Shaquiquzzaman, M.; Alam, M. M.; Akhter, M. Structure based virtual screening of MDPI database: discovery of structurally diverse and novel DPP-IV inhibitors Bioorg. Med. Chem. Lett. 2014, 24, 3447-3451 10.1016/j.bmcl.2014.05.076
247. Bavan, S.; Sherman, B.; Luetje, C. W.; Abaffy, T. Discovery of novel ligands for mouse olfactory receptor MOR42-3 using an in silico screening approach and in vitro validation PLoS One 2014, 9, e92064 10.1371/journal.pone.0092064
248. Murgueitio, M. S.; Henneke, P.; Glossmann, H.; Santos-Sierra, S.; Wolber, G. Prospective virtual screening in a sparse data scenario: design of small-molecule TLR2 antagonists ChemMedChem 2014, 9, 813-822 10.1002/cmdc.201300445
249. Stone, V. N.; Parikh, H. I.; El-Rami, F.; Ge, X.; Chen, W.; Zhang, Y.; Kellogg, G. E.; Xu, P. Identification of small-molecule inhibitors against meso-2, 6-diaminopimelate dehydrogenase from Porphyromonas gingivalis PLoS One 2015, 10, e0141126 10.1371/journal.pone.0141126
250. Zhong, H. J.; Liu, L. J.; Chong, C. M.; Lu, L.; Wang, M.; Chan, D. S.; Chan, P. W.; Lee, S. M.; Ma, D. L.; Leung, C. H. Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo PLoS One 2014, 9, e92905 10.1371/journal.pone.0092905
251. Mpamhanga, C. P.; Spinks, D.; Tulloch, L. B.; Shanks, E. J.; Robinson, D. A.; Collie, I. T.; Fairlamb, A. H.; Wyatt, P. G.; Frearson, J. A.; Hunter, W. N.; Gilbert, I. H.; Brenk, R. One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening J. Med. Chem. 2009, 52, 4454-4465 10.1021/jm900414x
252. Gschwend, D. A.; Sirawaraporn, W.; Santi, D. V.; Kuntz, I. D. Specificity in structure-based drug design: identification of a novel, selective inhibitor of Pneumocystis carinii dihydrofolate reductase Proteins: Struct., Funct., Genet. 1997, 29, 59-67 10.1002/(SICI)1097-0134(199709)29:1<59::AID-PROT4>3.0.CO;2-A
253. Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C. Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases J. Med. Chem. 1998, 41, 2588-2603 10.1021/jm980123i
254. Kobayashi, M.; Kinjo, T.; Koseki, Y.; Bourne, C. R.; Barrow, W. W.; Aoki, S. Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase J. Chem. Inf. Model. 2014, 54, 1242-1253 10.1021/ci400686d
255. McGovern, S. L.; Shoichet, B. K. Kinase inhibitors: not just for kinases anymore J. Med. Chem. 2003, 46, 1478-1483 10.1021/jm020427b
256. Huang, X. P.; Karpiak, J.; Kroeze, W. K.; Zhu, H.; Chen, X.; Moy, S. S.; Saddoris, K. A.; Nikolova, V. D.; Farrell, M. S.; Wang, S.; Mangano, T. J.; Deshpande, D. A.; Jiang, A.; Penn, R. B.; Jin, J.; Koller, B. H.; Kenakin, T.; Shoichet, B. K.; Roth, B. L. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65 Nature 2015, 527, 477-483 10.1038/nature15699