Identification of novel serotonin transporter compounds by virtual Screening

Journal of Chemical Information and Modeling

Volumn 54, Issue 3, 2014, Pages 933-943

  Gabrielsen, Mari ^a   Kurczab, Rafal ^b   Siwek, Agata ^c   Wolak, Malgorzata ^c   Ravna, Aina W ^a   Kristiansen, Kurt ^a   Kufareva, Irina ^d   Abagyan, Ruben ^d   Nowak, Gabriel ^b,c   Chilmonczyk, Zdzislaw ^e   Sylte, Ingebrigt ^a   Bojarski, Andrzej J ^b  

^a UNIVERSITY OF TROMSØ   (Norway)

^b INSTITUTE OF PHARMACOLOGY   (Poland)

^c JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^e NATIONAL MEDICINES INSTITUTE   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL ENGINEERING; CHEMISTRY;

HOMOLOGY MODELING; MULTIPLE CONFORMATIONS; PRE-SYNAPTIC NEURON; PSYCHOSTIMULANT DRUGS; SEROTONIN TRANSPORTERS; THREEDIMENSIONAL (3-D); TWO DIMENSIONAL (2 D); VIRTUAL SCREENING;

BINDERS;

PROTEIN BINDING; PSYCHOTROPIC AGENT; SEROTONIN TRANSPORTER;

BINDING SITE; CHEMISTRY; DRUG DATABASE; DRUG DEVELOPMENT; HUMAN; METABOLISM; MOLECULAR DOCKING;

BINDING SITES; DATABASES, PHARMACEUTICAL; DRUG DISCOVERY; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN BINDING; PSYCHOTROPIC DRUGS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 84897008974     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci400742s     Document Type: Article

References (80)

1. + symporters (NSS) aids in the use of the LeuT structure to probe NSS structure and function Mol. Pharmacol. 2006, 70, 1630-1642
2. Saier, M. H., Jr.; Tran, C. V.; Barabote, R. D. TCDB: The Transporter Classification Database for membrane transport protein analyses and information Nucleic Acids Res. 2006, 34, D181-186
3. Krishnamurthy, H.; Piscitelli, C. L.; Gouaux, E. Unlocking the molecular secrets of sodium-coupled transporters Nature 2009, 459, 347-355
4. Iversen, L. Neurotransmitter transporters: Fruitful targets for CNS drug discovery Mol. Psychiatry 2000, 5, 357-362
5. Rudnick, G. Bioenergetics of neurotransmitter transport J. Bioenerg. Biomembr. 1998, 30, 173-185
6. Quick, M.; Yano, H.; Goldberg, N. R.; Duan, L.; Beuming, T.; Shi, L.; Weinstein, H.; Javitch, J. A. State-dependent conformations of the translocation pathway in the tyrosine transporter Tyt1, a novel neurotransmitter:sodium symporter from Fusobacterium nucleatum J. Biol. Chem. 2006, 281, 26444-26454
7. Piscitelli, C. L.; Gouaux, E. Insights into transport mechanism from LeuT engineered to transport tryptophan EMBO J. 2012, 31, 228-235
8. Piscitelli, C. L.; Krishnamurthy, H.; Gouaux, E. Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site Nature 2010, 468, 1129-1132
9. Shi, L.; Quick, M.; Zhao, Y.; Weinstein, H.; Javitch, J. A. The mechanism of a neurotransmitter:sodium symporter - inward release of Na+ and substrate is triggered by substrate in a second binding site Mol. Cell 2008, 30, 667-677
10. Wang, H.; Elferich, J.; Gouaux, E. Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context Nat. Struct. Mol. Biol. 2012, 19, 212-219
11. Wang, H.; Gouaux, E. Substrate binds in the S1 site of the F253A mutant of LeuT, a neurotransmitter sodium symporter homologue EMBO Rep. 2012, 13, 861-866
12. Zhao, Y.; Terry, D.; Shi, L.; Weinstein, H.; Blanchard, S. C.; Javitch, J. A. Single-molecule dynamics of gating in a neurotransmitter transporter homologue Nature 2010, 465, 188-193
13. +-coupled neurotransmitter transporter homologue Nature 2011, 474, 109-113
14. Krishnamurthy, H.; Gouaux, E. X-ray structures of LeuT in substrate-free outward-open and apo inward-open states Nature 2012, 481, 469-474
15. Singh, S. K.; Piscitelli, C. L.; Yamashita, A.; Gouaux, E. A competitive inhibitor traps LeuT in an open-to-out conformation Science 2008, 322, 1655-1661
16. --dependent neurotransmitter transporters Nature 2005, 437, 215-223
17. Singh, S. K.; Yamashita, A.; Gouaux, E. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters Nature 2007, 448, 952-956
18. Zhou, Z.; Zhen, J.; Karpowich, N. K.; Goetz, R. M.; Law, C. J.; Reith, M. E.; Wang, D. N. LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake Science 2007, 317, 1390-1393
19. Zhou, Z.; Zhen, J.; Karpowich, N. K.; Law, C. J.; Reith, M. E.; Wang, D. N. Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures Nat. Struct. Mol. Biol. 2009, 16, 652-657
20. Kroncke, B. M.; Horanyi, P. S.; Columbus, L. Structural origins of nitroxide side chain dynamics on membrane protein alpha-helical sites Biochemistry 2010, 49, 10045-10060
21. Quick, M.; Winther, A. M.; Shi, L.; Nissen, P.; Weinstein, H.; Javitch, J. A. Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation Proc. Natl. Acad. Sci. USA. 2009, 106, 5563-5568
22. Penmatsa, A.; Wang, K. H.; Gouaux, E. X-ray structure of dopamine transporter elucidates antidepressant mechanism Nature 2013, 503, 85-90
23. Wang, H.; Goehring, A.; Wang, K. H.; Penmatsa, A.; Ressler, R.; Gouaux, E. Structural basis for action by diverse antidepressants on biogenic amine transporters Nature 2013, 503, 141-145
24. Ripphausen, P.; Nisius, B.; Peltason, L.; Bajorath, J. Quo vadis, virtual screening? A comprehensive survey of prospective applications J. Med. Chem. 2010, 53, 8461-8467
25. Wolber, G.; Seidel, T.; Bendix, F.; Langer, T. Molecule-pharmacophore superpositioning and pattern matching in computational drug design Drug Discovery Today 2008, 13, 23-29
26. Yang, S. Y. Pharmacophore modeling and applications in drug discovery: Challenges and recent advances Drug Discovery Today 2010, 15, 444-450
27. Enyedy, I. J.; Sakamuri, S.; Zaman, W. A.; Johnson, K. M.; Wang, S. Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors Bioorg. Med. Chem. Lett. 2003, 13, 513-517
28. Enyedy, I. J.; Wang, J.; Zaman, W. A.; Johnson, K. M.; Wang, S. Discovery of substituted 3,4-diphenyl-thiazoles as a novel class of monoamine transporter inhibitors through 3-D pharmacophore search using a new pharmacophore model derived from mazindol Bioorg. Med. Chem. Lett. 2002, 12, 1775-1778
29. Enyedy, I. J.; Zaman, W. A.; Sakamuri, S.; Kozikowski, A. P.; Johnson, K. M.; Wang, S. Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors Bioorg. Med. Chem. Lett. 2001, 11, 1113-1118
30. Indarte, M.; Liu, Y.; Madura, J. D.; Surratt, C. K. Receptor-Based Discovery of a Plasmalemmal Monoamine Transporter Inhibitor via High Throughput Docking and Pharmacophore Modeling ACS Chem. Neurosci. 2010, 1, 223-233
31. Kim, C. Y.; Mahaney, P. E.; McConnell, O.; Zhang, Y.; Manas, E.; Ho, D. M.; Deecher, D. C.; Trybulski, E. J. Discovery of a new series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols Bioorg. Med. Chem. Lett. 2009, 19, 5029-5032
32. Kiss, R.; Sandor, M.; Gere, A.; Schmidt, E.; Balogh, G. T.; Kiss, B.; Molnar, L.; Lemmen, C.; Keseru, G. M. Discovery of novel histamine H4 and serotonin transporter ligands using the topological feature tree descriptor J. Chem. Inf. Model. 2012, 52, 233-242
33. Manepalli, S.; Geffert, L. M.; Surratt, C. K.; Madura, J. D. Discovery of novel selective serotonin reuptake inhibitors through development of a protein-based pharmacophore J. Chem. Inf. Model. 2011, 51, 2417-2426
34. Nolan, T. L.; Lapinsky, D. J.; Talbot, J. N.; Indarte, M.; Liu, Y.; Manepalli, S.; Geffert, L. M.; Amos, M. E.; Taylor, P. N.; Madura, J. D.; Surratt, C. K. Identification of a novel selective serotonin reuptake inhibitor by coupling monoamine transporter-based virtual screening and rational molecular hybridization ACS Chem. Neurosci. 2011, 2, 544-552
35. Schlessinger, A.; Geier, E.; Fan, H.; Irwin, J. J.; Shoichet, B. K.; Giacomini, K. M.; Sali, A. Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET Proc. Natl. Acad. Sci. USA. 2011, 108, 15810-15815
36. Wang, S.; Sakamuri, S.; Enyedy, I. J.; Kozikowski, A. P.; Deschaux, O.; Bandyopadhyay, B. C.; Tella, S. R.; Zaman, W. A.; Johnson, K. M. Discovery of a novel dopamine transporter inhibitor, 4-hydroxy-1-methyl-4-(4-methylphenyl)-3- piperidyl 4-methylphenyl ketone, as a potential cocaine antagonist through 3D-database pharmacophore searching. Molecular modeling, structure-activity relationships, and behavioral pharmacological studies J. Med. Chem. 2000, 43, 351-360
37. Macdougall, I. J.; Griffith, R. Pharmacophore design and database searching for selective monoamine neurotransmitter transporter ligands J. Mol. Graph. Model. 2008, 26, 1113-1124
38. Kortagere, S.; Fontana, A. C.; Rose, D. R.; Mortensen, O. V. Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action Neuropharmacology 2013, 72, 282-290
39. Gabrielsen, M.; Kurczab, R.; Ravna, A. W.; Kufareva, I.; Abagyan, R.; Chilmonczyk, Z.; Bojarski, A. J.; Sylte, I. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol Eur. J. Med. Chem. 2012, 47, 24-37
40. Asinex Home Page, www.asinex.com (accessed 2010).
41. ChemBridge Home Page, www.chembridge.com (accessed 2010).
42. ChemDiv Home Page, www.chemdiv.com (accessed 2010).
43. Enamine Home Page, www.enamine.net (accessed 2010).
44. Life Chemicals Home Page, www.lifechemicals.com (accessed 2010).
45. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 2001, 46, 3-26
46. Veber, D. F.; Johnson, S. R.; Cheng, H. Y.; Smith, B. R.; Ward, K. W.; Kopple, K. D. Molecular properties that influence the oral bioavailability of drug candidates J. Med. Chem. 2002, 45, 2615-2623
47. JChem version 5.3.1, ChemAxon (http://www.chemaxon.com).
48. 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
49. Marvin, version 5.3.1, ChemAxon (http://www.chemaxon.com).
50. QikProp, version 3.2; Schrödinger LLC: New York, 2010.
51. D.S.M.E., Release 2.5; Accelrys Software, Inc.: San Diego, CA, 2010.
52. Beutler, T. C.; Dill, K. A. A fast conformational search strategy for finding low energy structures of model proteins Protein Sci. 1996, 5, 2037-2043
53. Barnum, D.; Greene, J.; Smellie, A.; Sprague, P. Identification of common functional configurations among molecules J. Chem. Inf. Comput. Sci. 1996, 36, 563-571
54. Instant JChem, version 5.3.1; ChemAxon (http://www.chemaxon.com).
55. Abagyan, R.; Totrov, M.; Kuznetsov, D. ICM - A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation J. Comput. Chem. 1994, 15, 488-506
56. An, J.; Totrov, M.; Abagyan, R. Pocketome via comprehensive identification and classification of ligand binding envelopes Mol. Cell Proteomics 2005, 4, 752-761
57. Abagyan, R.; Totrov, M. Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins J. Mol. Biol. 1994, 235, 983-1002
58. Bottegoni, G.; Kufareva, I.; Totrov, M.; Abagyan, R. Four-dimensional docking: A fast and accurate account of discrete receptor flexibility in ligand docking J. Med. Chem. 2009, 52, 397-406
59. Canvas software; Schrödinger LLC: New York, 2010.
60. Wrobel, M. Z.; Chodkowski, A.; Herold, F.; Gomolka, A.; Kleps, J.; Mazurek, A. P.; Plucinski, F.; Mazurek, A.; Nowak, G.; Siwek, A.; Stachowicz, K.; Slawinska, A.; Wolak, M.; Szewczyk, B.; Satala, G.; Bojarski, A. J.; Turlo, J. Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1 Eur. J. Med. Chem. 2013, 63, 484-500
61. 50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22, 3099-3108
62. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B.; Overington, J. P. ChEMBL: A large-scale bioactivity database for drug discovery Nucleic Acids Res. 2012, 40, D1100-D1107
63. Andersen, J.; Olsen, L.; Hansen, K. B.; Taboureau, O.; Jorgensen, F. S.; Jorgensen, A. M.; Bang-Andersen, B.; Egebjerg, J.; Stromgaard, K.; Kristensen, A. S. Mutational mapping and modeling of the binding site for (S)-citalopram in the human serotonin transporter J. Biol. Chem. 2010, 285, 2051-2063
64. Barker, E. L.; Moore, K. R.; Rakhshan, F.; Blakely, R. D. Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter J. Neurosci. 1999, 19, 4705-4717
65. Celik, L.; Sinning, S.; Severinsen, K.; Hansen, C. G.; Moller, M. S.; Bols, M.; Wiborg, O.; Schiott, B. Binding of serotonin to the human serotonin transporter. Molecular modeling and experimental validation J. Am. Chem. Soc. 2008, 130, 3853-3865
66. Sinning, S.; Musgaard, M.; Jensen, M.; Severinsen, K.; Celik, L.; Koldso, H.; Meyer, T.; Bols, M.; Jensen, H. H.; Schiott, B.; Wiborg, O. Binding and orientation of tricyclic antidepressants within the central substrate site of the human serotonin transporter J. Biol. Chem. 2010, 285, 8363-8374
67. Chuprina, A.; Lukin, O.; Demoiseaux, R.; Buzko, A.; Shivanyuk, A. Drug- and lead-likeness, target class, and molecular diversity analysis of 7.9 million commercially available organic compounds provided by 29 suppliers J. Chem. Inf. Model. 2010, 50, 470-479
68. Dodd, J. R.; Christie, D. L. Selective amino acid substitutions convert the creatine transporter to a gamma-aminobutyric acid transporter J. Biol. Chem. 2007, 282, 15528-15533
69. Stockner, T.; Montgomery, T. R.; Kudlacek, O.; Weissensteiner, R.; Ecker, G. F.; Freissmuth, M.; Sitte, H. H. Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model PLoS Comput. Biol. 2013, 9, e1002909
70. Forrest, L. R.; Zhang, Y. W.; Jacobs, M. T.; Gesmonde, J.; Xie, L.; Honig, B. H.; Rudnick, G. Mechanism for alternating access in neurotransmitter transporters Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 10338-10343
71. Tavoulari, S.; Forrest, L. R.; Rudnick, G. Fluoxetine (Prozac) binding to serotonin transporter is modulated by chloride and conformational changes J. Neurosci. 2009, 29, 9635-9643
72. Torres-Altoro, M. I.; Kuntz, C. P.; Nichols, D. E.; Barker, E. L. Structural analysis of the extracellular entrance to the serotonin transporter permeation pathway J. Biol. Chem. 2010, 285, 15369-15379
73. Zhang, Y. W.; Rudnick, G. The cytoplasmic substrate permeation pathway of serotonin transporter J. Biol. Chem. 2006, 281, 36213-36220
74. Rothman, R. B.; Baumann, M. H.; Blough, B. E.; Jacobson, A. E.; Rice, K. C.; Partilla, J. S. Evidence for noncompetitive modulation of substrate-induced serotonin release Synapse 2010, 64, 862-869
75. Rueda, M.; Totrov, M.; Abagyan, R. ALiBERO: Evolving a team of complementary pocket conformations rather than a single leader J. Chem. Inf. Model. 2012, 52, 2705-2714
76. Totrov, M.; Abagyan, R. Flexible ligand docking to multiple receptor conformations: A practical alternative Curr. Opin. Struct. Biol. 2008, 18, 178-184
77. Huang, S. Y.; Grinter, S. Z.; Zou, X. Scoring functions and their evaluation methods for protein-ligand docking: Recent advances and future directions Phys. Chem. Chem. Phys. 2010, 12, 12899-12908
78. Owens, M. J.; Knight, D. L.; Nemeroff, C. B. Second-generation SSRIs: Human monoamine transporter binding profile of escitalopram and R-fluoxetine Biol. Psychiatry 2001, 50, 345-350
79. Owens, M. J.; Morgan, W. N.; Plott, S. J.; Nemeroff, C. B. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites J. Pharmacol. Exp. Ther. 1997, 283, 1305-1322
80. Adkins, E. M.; Barker, E. L.; Blakely, R. D. Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition Mol. Pharmacol. 2001, 59, 514-523