Discovery of GPCR ligands by molecular docking screening: Novel opportunities provided by crystal structures

Current Topics in Medicinal Chemistry

Volumn 15, Issue 24, 2015, Pages 2484-2503

  Rodríguez, David ^a,b,c   Ranganathan, Anirudh ^a,b,c   Carlsson, Jens ^a,b,c  

^a SCIENCE FOR LIFE LABORATORY   (Sweden)

^b Linköping University   (Sweden)

^c STOCKHOLM UNIVERSITY   (Sweden)

Author keywords

Agonist; Allosteric modulation; Drug discovery; Fragment based lead discovery; G protein coupled receptors; Library bias; Selectivity; Virtual screening

Indexed keywords

ACETYLCHOLINE; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR BLOCKING AGENT; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; ENDORPHIN; EPSILON OPIATE RECEPTOR; ERGOTAMINE; G PROTEIN COUPLED RECEPTOR LIGAND; GLUCAGON; GLUTAMIC ACID; LIGAND; NEUROKININ 1 RECEPTOR; NEUROTENSIN; OREXIN; PURINERGIC P2Y12 RECEPTOR; SEROTONIN 1B RECEPTOR; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG; G PROTEIN COUPLED RECEPTOR;

ARTICLE; BINDING SITE; CRYSTAL STRUCTURE; DRUG DEVELOPMENT; HUMAN; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR DYNAMICS; POLYPHARMACOLOGY; CHEMICAL STRUCTURE; METABOLISM;

DRUG DISCOVERY; HUMANS; LIGANDS; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84942133514     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026615666150701112853     Document Type: Article

References (161)

1. Lagerstrom, M.C., Schioth, H.B. Structural Diversity of G Protein-Coupled Receptors and Significance for Drug Discovery. Nat. Rev. Drug Discovery, 2008, 7, 339-357.
2. Attwood, T.K., Findlay, J.B. Fingerprinting G-Protein-Coupled Receptors. Protein Eng., 1994, 7, 195-203.
3. Fredriksson, R.; Lagerstrom, M.C.; Lundin, L.-G., Schioth, H.B. The G-Protein-Coupled Receptors in the Human Genome Form Five Main Families. Phylogenetic Analysis, Paralogon Groups, and Fingerprints. Mol. Pharmacol., 2003, 63, 1256-1272.
4. Alexander, S.P.; Benson, H.E.; Faccenda, E.; Pawson, A.J.; Sharman, J.L.; Spedding, M.; Peters, J.A.; Harmar, A.J., Collaborators, C. The Concise Guide to Pharmacology 2013/14: G Protein-Coupled Receptors. Br. J. Pharmacol., 2013, 170, 1459-1581.
5. Overington, J.P.; Al-Lazikani, B., Hopkins, A.L. How Many Drug Targets Are There? Nat. Rev. Drug Discovery, 2006, 5, 993-996.
6. Rosenbaum, D.M.; Rasmussen, S.G., Kobilka, B.K. The Structure and Function of G-Protein-Coupled Receptors. Nature, 2009, 459, 356-363.
7. Katritch, V.; Cherezov, V., Stevens, R.C. Structure-Function of the G Protein-Coupled Receptor Superfamily. Annu. Rev. Pharmacol. Toxicol, 2013, 53, 531-556.
8. Deupi, X., Kobilka, B.K. Energy Landscapes as a Tool to Integrate GPCR Structure, Dynamics, and Function. Physiology, 2010, 25, 293-303.
9. Violin, J.D.; Crombie, A.L.; Soergel, D.G., Lark, M.W. Biased Ligands at G-Protein-Coupled Receptors: Promise and Progress. Trends Pharmacol. Sci., 2014, 35, 308-316.
10. Roth, B.L.; Sheffler, D.J., Kroeze, W.K. Magic Shotguns Versus Magic Bullets: Selectively Non-Selective Drugs for Mood Disorders and Schizophrenia. Nat. Rev. Drug Discovery, 2004, 3, 353-359.
11. Jorg, M.; Scammells, P.J., Capuano, B. The Dopamine D2 and Adenosine A2A Receptors: Past, Present and Future Trends for the Treatment of Parkinson's Disease. Curr. Med. Chem., 2014, 21, 3188-3210.
12. Christopoulos, A. Advances in G Protein-Coupled Receptor Allostery: From Function to Structure. Mol. Pharmacol., 2014, 86, 463-478.
13. Venkatakrishnan, A.J.; Deupi, X.; Lebon, G.; Tate, C.G.; Schertler, G.F., Babu, M.M. Molecular Signatures of G-Protein-Coupled Receptors. Nature, 2013, 494, 185-194.
14. Zhang, X.; Stevens, R.C., Xu, F. The Importance of Ligands for G Protein-Coupled Receptor Stability. Trends Biochem. Sci, 2015, 40, 79-87.
15. Kooistra, A.J.; de Graaf, C., Timmerman, H. The Receptor Concept in 3d: From Hypothesis and Metaphor to GPCR-Ligand Structures. Neurochem. Res., 2014, 39, 1850-1861.
16. Rosenbaum, D.M.; Cherezov, V.; Hanson, M.A.; Rasmussen, S.G.F.; Thian, F.S.; Kobilka, T.S.; Choi, H.-J.; Yao, X.-J.; Weis, W.I.; Stevens, R.C., Kobilka, B.K. GPCR Engineering Yields High-Resolution Structural Insights into Beta2-Adrenergic Receptor Function. Science, 2007, 318, 1266-1273.
17. Rasmussen, S.G.; Choi, H.J.; Fung, J.J.; Pardon, E.; Casarosa, P.; Chae, P.S.; Devree, B.T.; Rosenbaum, D.M.; Thian, F.S.; Kobilka, T.S.; Schnapp, A.; Konetzki, I.; Sunahara, R.K.; Gellman, S.H.; Pautsch, A.; Steyaert, J.; Weis, W.I., Kobilka, B.K. Structure of a Nanobody-Stabilized Active State of the Beta2 Adrenoceptor. Nature, 2011, 469, 175-180.
18. Jaakola, V.-P.; Griffith, M.T.; Hanson, M.A.; Cherezov, V.; Chien, E.Y.T.; Lane, J.R.; Ijzerman, A.P., Stevens, R.C. The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist. Science, 2008, 322, 1211-1217.
19. Warne, T.; Serrano-Vega, M.J.; Baker, J.G.; Moukhametzianov, R.; Edwards, P.C.; Henderson, R.; Leslie, A.G.W.; Tate, C.G., Schertler, G.F.X. Structure of a Beta1-Adrenergic G-Protein-Coupled Receptor. Nature, 2008, 454, 486-491.
20. Wang, C.; Jiang, Y.; Ma, J.; Wu, H.; Wacker, D.; Katritch, V.; Han, G.W.; Liu, W.; Huang, X.P.; Vardy, E.; McCorvy, J.D.; Gao, X.; Zhou, X.E.; Melcher, K.; Zhang, C.; Bai, F.; Yang, H.; Yang, L.; Jiang, H.; Roth, B.L.; Cherezov, V.; Stevens, R.C., Xu, H.E. Structural Basis for Molecular Recognition at Serotonin Receptors. Science, 2013, 340, 610-614.
21. Chien, E.Y.T.; Liu, W.; Zhao, Q.; Katritch, V.; Han, G.W.; Hanson, M.A.; Shi, L.; Newman, A.H.; Javitch, J.A.; Cherezov, V., Stevens, R.C. Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist. Science, 2010, 330, 1091-1095.
22. Shimamura, T.; Shiroishi, M.; Weyand, S.; Tsujimoto, H.; Winter, G.; Katritch, V.; Abagyan, R.; Cherezov, V.; Liu, W.; Han, G.W.; Kobayashi, T.; Stevens, R.C., Iwata, S. Structure of the Human Histamine H1 Receptor Complex with Doxepin. Nature, 2011, 475, 65-70.
23. Haga, K.; Kruse, A.C.; Asada, H.; Yurugi-Kobayashi, T.; Shiroishi, M.; Zhang, C.; Weis, W.I.; Okada, T.; Kobilka, B.K.; Haga, T., Kobayashi, T. Structure of the Human M2 Muscarinic Acetylcholine Receptor Bound to an Antagonist. Nature, 2012, 482, 547-551.
24. Kruse, A.C.; Hu, J.; Pan, A.C.; Arlow, D.H.; Rosenbaum, D.M.; Rosemond, E.; Green, H.F.; Liu, T.; Chae, P.S.; Dror, R.O.; Shaw, D.E.; Weis, W.I.; Wess, J., Kobilka, B.K. Structure and Dynamics of the M3 Muscarinic Acetylcholine Receptor. Nature, 2012, 482, 552-556.
25. Zhang, K.; Zhang, J.; Gao, Z.G.; Zhang, D.; Zhu, L.; Han, G.W.; Moss, S.M.; Paoletta, S.; Kiselev, E.; Lu, W.; Fenalti, G.; Zhang, W.; Muller, C.E.; Yang, H.; Jiang, H.; Cherezov, V.; Katritch, V.; Jacobson, K.A.; Stevens, R.C.; Wu, B., Zhao, Q. Structure of the Human P2Y12 Receptor in Complex with an Antithrombotic Drug. Nature, 2014, 509, 115-118.
26. Wu, B.; Chien, E.Y.; Mol, C.D.; Fenalti, G.; Liu, W.; Katritch, V.; Abagyan, R.; Brooun, A.; Wells, P.; Bi, F.C.; Hamel, D.J.; Kuhn, P.; Handel, T.M.; Cherezov, V., Stevens, R.C. Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists. Science, 2010, 330, 1066-1071.
27. Tan, Q.; Zhu, Y.; Li, J.; Chen, Z.; Han, G.W.; Kufareva, I.; Li, T.; Ma, L.; Fenalti, G.; Li, J.; Zhang, W.; Xie, X.; Yang, H.; Jiang, H.; Cherezov, V.; Liu, H.; Stevens, R.C.; Zhao, Q., Wu, B. Structure of the CCR5 Chemokine Receptor-Hiv Entry Inhibitor Maraviroc Complex. Science, 2013, 341, 1387-1390.
28. Thompson, A.A.; Liu, W.; Chun, E.; Katritch, V.; Wu, H.; Vardy, E.; Huang, X.-P.; Trapella, C.; Guerrini, R.; Calo, G.; Roth, B.L.; Cherezov, V., Stevens, R.C. Structure of the Nociceptin/Orphanin FQ Receptor in Complex with a Peptide Mimetic. Nature, 2012, 485, 395-399.
29. Manglik, A.; Kruse, A.C.; Kobilka, T.S.; Thian, F.S.; Mathiesen, J.M.; Sunahara, R.K.; Pardo, L.; Weis, W.I.; Kobilka, B.K., Granier, S. Crystal Structure of the Mu-Opioid Receptor Bound to a Morphinan Antagonist. Nature, 2012, 485, 321-326.
30. Wu, H.; Wacker, D.; Mileni, M.; Katritch, V.; Han, G.W.; Vardy, E.; Liu, W.; Thompson, A.A.; Huang, X.P.; Carroll, F.I.; Mascarella, S.W.; Westkaemper, R.B.; Mosier, P.D.; Roth, B.L.; Cherezov, V., Stevens, R.C. Structure of the Human Kappa-Opioid Receptor in Complex with Jdtic. Nature, 2012, 485, 327-332.
31. Granier, S.; Manglik, A.; Kruse, A.C.; Kobilka, T.S.; Thian, F.S.; Weis, W.I., Kobilka, B.K. Structure of the Delta-Opioid Receptor Bound to Naltrindole. Nature, 2012, 485, 400-404.
32. White, J.F.; Noinaj, N.; Shibata, Y.; Love, J.; Kloss, B.; Xu, F.; Gvozdenovic-Jeremic, J.; Shah, P.; Shiloach, J.; Tate, C.G., Grisshammer, R. Structure of the Agonist-Bound Neurotensin Receptor. Nature, 2012, 490, 508-513.
33. Zhang, C.; Srinivasan, Y.; Arlow, D.H.; Fung, J.J.; Palmer, D.; Zheng, Y.; Green, H.F.; Pandey, A.; Dror, R.O.; Shaw, D.E.; Weis, W.I.; Coughlin, S.R., Kobilka, B.K. High-Resolution Crystal Structure of Human Protease-Activated Receptor 1. Nature, 2012, 492, 387-392.
34. Yin, J.; Mobarec, J.C.; Kolb, P., Rosenbaum, D.M. Crystal Structure of the Human OX Orexin Receptor Bound to the Insomnia Drug Suvorexant. Nature, 2014, 519, 247-250.
35. Hanson, M.A.; Roth, C.B.; Jo, E.; Griffith, M.T.; Scott, F.L.; Reinhart, G.; Desale, H.; Clemons, B.; Cahalan, S.M.; Schuerer, S.C.; Sanna, M.G.; Han, G.W.; Kuhn, P.; Rosen, H., Stevens, R.C. Crystal Structure of a Lipid G Protein-Coupled Receptor. Science, 2012, 335, 851-855.
36. Srivastava, A.; Yano, J.; Hirozane, Y.; Kefala, G.; Gruswitz, F.; Snell, G.; Lane, W.; Ivetac, A.; Aertgeerts, K.; Nguyen, J.; Jennings, A., Okada, K. High-Resolution Structure of the Human GPR40 Receptor Bound to Allosteric Agonist Tak-875. Nature, 2014, 513, 124-127.
37. Siu, F.Y.; He, M.; de Graaf, C.; Han, G.W.; Yang, D.; Zhang, Z.; Zhou, C.; Xu, Q.; Wacker, D.; Joseph, J.S.; Liu, W.; Lau, J.; Cherezov, V.; Katritch, V.; Wang, M.W., Stevens, R.C. Structure of the Human Glucagon Class B G-Protein-Coupled Receptor. Nature, 2013, 499, 444-449.
38. Hollenstein, K.; Kean, J.; Bortolato, A.; Cheng, R.K.; Dore, A.S.; Jazayeri, A.; Cooke, R.M.; Weir, M., Marshall, F.H. Structure of Class B GPCR Corticotropin-Releasing Factor Receptor 1. Nature, 2013, 499, 438-443.
39. Wu, H.; Wang, C.; Gregory, K.J.; Han, G.W.; Cho, H.P.; Xia, Y.; Niswender, C.M.; Katritch, V.; Meiler, J.; Cherezov, V.; Conn, P.J., Stevens, R.C. Structure of a Class C GPCR Metabotropic Glutamate Receptor 1 Bound to an Allosteric Modulator. Science, 2014, 344, 58-64.
40. Dore, A.S.; Okrasa, K.; Patel, J.C.; Serrano-Vega, M.; Bennett, K.; Cooke, R.M.; Errey, J.C.; Jazayeri, A.; Khan, S.; Tehan, B.; Weir, M.; Wiggin, G.R., Marshall, F.H. Structure of Class C GPCR Metabotropic Glutamate Receptor 5 Transmembrane Domain. Nature, 2014, 511, 557-562.
41. Wang, C.; Wu, H.; Katritch, V.; Han, G.W.; Huang, X.P.; Liu, W.; Siu, F.Y.; Roth, B.L.; Cherezov, V., Stevens, R.C. Structure of the Human Smoothened Receptor Bound to an Antitumour Agent. Nature, 2013, 497, 338-343.
42. Wang, C.; Wu, H.; Evron, T.; Vardy, E.; Han, G.W.; Huang, X.P.; Hufeisen, S.J.; Mangano, T.J.; Urban, D.J.; Katritch, V.; Cherezov, V.; Caron, M.G.; Roth, B.L., Stevens, R.C. Structural Basis for Smoothened Receptor Modulation and Chemoresistance to Anticancer Drugs. Nat. Commun., 2014, 5, 4355.
43. Lebon, G.; Warne, T., Tate, C.G. Agonist-Bound Structures of G Protein-Coupled Receptors. Curr. Opin. Struct. Biol., 2012, 22, 482-490.
44. Rasmussen, S.G.; DeVree, B.T.; Zou, Y.; Kruse, A.C.; Chung, K.Y.; Kobilka, T.S.; Thian, F.S.; Chae, P.S.; Pardon, E.; Calinski, D.; Mathiesen, J.M.; Shah, S.T.; Lyons, J.A.; Caffrey, M.; Gellman, S.H.; Steyaert, J.; Skiniotis, G.; Weis, W.I.; Sunahara, R.K., Kobilka, B.K. Crystal Structure of the Beta2 Adrenergic Receptor-Gs Protein Complex. Nature, 2011, 477, 549-555.
45. 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.
46. Warne, T.; Moukhametzianov, R.; Baker, J.G.; Nehme, R.; Edwards, P.C.; Leslie, A.G.; Schertler, G.F., Tate, C.G. The Structural Basis for Agonist and Partial Agonist Action on a Beta1-Adrenergic Receptor. Nature, 2011, 469, 241-244.
47. Xu, F.; Wu, H.; Katritch, V.; Han, G.W.; Jacobson, K.A.; Gao, Z.G.; Cherezov, V., Stevens, R.C. Structure of an Agonist-Bound Human A2A Adenosine Receptor. Science, 2011, 332
48. Lebon, G.; Warne, T.; Edwards, P.C.; Bennett, K.; Langmead, C.J.; Leslie, A.G., Tate, C.G. Agonist-Bound Adenosine A2A Receptor Structures Reveal Common Features of GPCR Activation. Nature, 2011, 474, 521-525.
49. Kruse, A.C.; Ring, A.M.; Manglik, A.; Hu, J.; Hu, K.; Eitel, K.; Hubner, H.; Pardon, E.; Valant, C.; Sexton, P.M.; Christopoulos, A.; Felder, C.C.; Gmeiner, P.; Steyaert, J.; Weis, W.I.; Garcia, K.C.; Wess, J., Kobilka, B.K. Activation and Allosteric Modulation of a Muscarinic Acetylcholine Receptor. Nature, 2013, 504, 101-106.
50. Zhang, J.; Zhang, K.; Gao, Z.G.; Paoletta, S.; Zhang, D.; Han, G.W.; Li, T.; Ma, L.; Zhang, W.; Muller, C.E.; Yang, H.; Jiang, H.; Cherezov, V.; Katritch, V.; Jacobson, K.A.; Stevens, R.C.; Wu, B., Zhao, Q. Agonist-Bound Structure of the Human P2Y12 Receptor. Nature, 2014, 509, 119-122.
51. Warne, T.; Edwards, P.C.; Leslie, A.G., Tate, C.G. Crystal Structures of a Stabilized Beta1-Adrenoceptor Bound to the Biased Agonists Bucindolol and Carvedilol. Structure, 2012, 20, 841-849.
52. Wacker, D.; Wang, C.; Katritch, V.; Han, G.W.; Huang, X.P.; Vardy, E.; McCorvy, J.D.; Jiang, Y.; Chu, M.; Siu, F.Y.; Liu, W.; Xu, H.E.; Cherezov, V.; Roth, B.L., Stevens, R.C. Structural Features for Functional Selectivity at Serotonin Receptors. Science, 2013, 340, 615-619.
53. Zhang, D.; Gao, Z.G.; Zhang, K.; Kiselev, E.; Crane, S.; Wang, J.; Paoletta, S.; Yi, C.; Ma, L.; Zhang, W.; Han, G.W.; Liu, H.; Cherezov, V.; Katritch, V.; Jiang, H.; Stevens, R.C.; Jacobson, K.A.; Zhao, Q., Wu, B. Two Disparate Ligand-Binding Sites in the Human P2Y1 Receptor. Nature, 2015, 520, 317-321.
54. Miller-Gallacher, J.L.; Nehme, R.; Warne, T.; Edwards, P.C.; Schertler, G.F.; Leslie, A.G., Tate, C.G. The 2.1 a Resolution Structure of Cyanopindolol-Bound Beta1-Adrenoceptor Identifies an Intramembrane Na+ Ion That Stabilises the Ligand-Free Receptor. PLoS One, 2014, 9, e92727.
55. Liu, W.; Chun, E.; Thompson, A.A.; Chubukov, P.; Xu, F.; Katritch, V.; Han, G.W.; Roth, C.B.; Heitman, L.H.; IJzerman, A.P.; Cherezov, V., Stevens, R.C. Structural Basis for Allosteric Regulation of GPCRS by Sodium Ions. Science, 2012, 337, 232-236.
56. Fenalti, G.; Giguere, P.M.; Katritch, V.; Huang, X.P.; Thompson, A.A.; Cherezov, V.; Roth, B.L., Stevens, R.C. Molecular Control of Delta-Opioid Receptor Signalling. Nature, 2014, 506, 191-196.
57. Chun, L.; Zhang, W.H., Liu, J.F. Structure and Ligand Recognition of Class C Gpcrs. Acta Pharmacol. Sin. 2012, 33, 312-323.
58. Shoichet, B.K. Virtual Screening of Chemical Libraries. Nature, 2004, 432, 862-865.
59. Kitchen, D.B.; Decornez, H.; Furr, J.R., Bajorath, J. Docking and Scoring in Virtual Screening for Drug Discovery: Methods and Applications. Nature Rev. Drug Discovery, 2004, 3, 935-949.
60. Shoichet, B.K., Kobilka, B.K. Structure-Based Drug Screening for G-Protein-Coupled Receptors. Trends Pharmacol. Sci., 2012, 33, 268-272.
61. Kooistra, A.J.; Roumen, L.; Leurs, R.; de Esch, I.J., de Graaf, C. From Heptahelical Bundle to Hits from the Haystack: Structure-Based Virtual Screening for GPCR Ligands. Methods Enzymol., 2013, 522, 279-336.
62. Rodriguez, D., Gutierrez-de-Teran, H. Computational Approaches for Ligand Discovery and Design in Class-A G Protein-Coupled Receptors. Curr. Pharm. Des., 2013, 19, 2216-2236.
63. Deupi, X., Standfuss, J. Structural Insights into Agonist-Induced Activation of G-Protein-Coupled Receptors. Curr. Opin. Struct. Biol., 2011, 21, 541-551.
64. Sabio, M.; Jones, K., Topiol, S. Use of the X-Ray Structure of the Beta2-Adrenergic Receptor for Drug Discovery. Part 2: Identification of Active Compounds. Bioorg. Med. Chem. Lett., 2008, 18, 5391-5395.
65. 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. USA., 2009, 106, 6843-6848.
66. Halgren, T.A.; Murphy, R.B.; Friesner, R.A.; Beard, H.S.; Frye, L.L.; Pollard, W.T., Banks, J.L. Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening. J. Med. Chem., 2004, 47, 1750-1759.
67. Lorber, D.M., Shoichet, B.K. Hierarchical Docking of Databases of Multiple Ligand Conformations. Curr. Top. Med. Chem., 2005, 5, 739-749.
68. 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.
69. 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.
70. Neves, M.A.; Totrov, M., Abagyan, R. Docking and Scoring with Icm: The Benchmarking Results and Strategies for Improvement. J. Comput.-Aided Mol. Des., 2012, 26, 675-686.
71. Armentero, M.T.; Pinna, A.; Ferre, S.; Lanciego, J.L.; Muller, C.E., Franco, R. Past, Present and Future of A(2A) Adenosine Receptor Antagonists in the Therapy of Parkinson's Disease. Pharmacol. Ther., 2011, 132, 280-299.
72. Irwin, J.J.; Sterling, T.; Mysinger, M.M.; Bolstad, E.S., Coleman, R.G. ZINC -a Free Tool to Discover Chemistry for Biology. J. Chem. Inf. Model, 2012, 52, 1757-1768.
73. 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.
74. Choi, W.T.; Duggineni, S.; Xu, Y.; Huang, Z., An, J. Drug Discovery Research Targeting the CXC Chemokine Receptor 4 (CXCR4). J. Med. Chem., 2011, 55, 977-994.
75. Mysinger, M.M.; Weiss, D.R.; Ziarek, J.J.; Gravel, S.; Doak, A.K.; Karpiak, J.; Heveker, N.; Shoichet, B.K., Volkman, B.F. Structure-Based Ligand Discovery for the Protein-Protein Interface of Chemokine Receptor CXCR4. Proc. Natl. Acad. Sci. USA., 2012, 109, 5517-5522.
76. Hert, J.; Irwin, J.J.; Laggner, C.; Keiser, M.J., Shoichet, B.K. Quantifying Biogenic Bias in Screening Libraries. Nat. Chem. Biol., 2009, 5, 479-483.
77. Keiser, M.J.; Roth, B.L.; Armbruster, B.N.; Ernsberger, P.; Irwin, J.J., Shoichet, B.K. Relating Protein Pharmacology by Ligand Chemistry. Nat. Biotechnol., 2007, 25, 197-206.
78. Negri, A.; Rives, M.L.; Caspers, M.J.; Prisinzano, T.E.; Javitch, J.A., Filizola, M. Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening. J. Chem. Inf. Model., 2013, 53, 512-526.
79. 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 H1 Receptor. J. Med. Chem., 2011, 54, 8195-8206.
80. Kruse, A.C.; Weiss, D.R.; Rossi, M.; Hu, J.; Hu, K.; Eitel, K.; Gmeiner, P.; Wess, J.; Kobilka, B.K., Shoichet, B.K. Muscarinic Receptors as Model Targets and Antitargets for Structure-Based Ligand Discovery. Mol. Pharmacol., 2013, 84, 528-540.
81. Weiss, D.R.; Ahn, S.; Sassano, M.F.; Kleist, A.; Zhu, X.; Strachan, R.; Roth, B.L.; Lefkowitz, R.J., Shoichet, B.K. Conformation Guides Molecular Efficacy in Docking Screens of Activated Beta-2 Adrenergic G Protein Coupled Receptor. ACS Chem. Biol., 2013, 8, 1018-1026.
82. Rodriguez, D.; Brea, J.; Loza, M.I., Carlsson, J. Structure-Based Discovery of Selective Serotonin 5-HT1B Ligands. Structure, 2014, 22, 1140-1151.
83. 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.
84. Strader, C.D.; Candelore, M.R.; Hill, W.S.; Sigal, I.S., Dixon, R.A. Identification of Two Serine Residues Involved in Agonist Activation of the Beta-Adrenergic Receptor. J. Biol. Chem., 1989, 264, 13572-13578.
85. Liapakis, G.; Ballesteros, J.A.; Papachristou, S.; Chan, W.C.; Chen, X., Javitch, J.A. The Forgotten Serine. A Critical Role for Ser-2035.42 in Ligand Binding to and Activation of the Beta2-Adrenergic Receptor. J. Biol. Chem., 2000, 275, 37779-37788.
86. Ballesteros, J.A., Weinstein, H. Integrated Methods for the Construction of Three Dimensional Models and Computational Probing of Structure-Function Relations in G-Protein Coupled Receptors. Methods Neurosci., 1995, 25, 366-428.
87. de Graaf, C., Rognan, D. Selective Structure-Based Virtual Screening for Full and Partial Agonists of the Beta2 Adrenergic Receptor. J. Med. Chem., 2008, 51, 4978-4985.
88. Katritch, V.; Reynolds, K.A.; Cherezov, V.; Hanson, M.A.; Roth, C.B.; Yeager, M., Abagyan, R. Analysis of Full and Partial Agonists Binding to Beta2-Adrenergic Receptor Suggests a Role of Transmembrane Helix V in Agonist-Specific Conformational Changes. J. Mol. Recognit., 2009, 22, 307-318.
89. Mysinger, M.M., Shoichet, B.K. Rapid Context-Dependent Ligand Desolvation in Molecular Docking. J. Chem. Inf. Model., 2010, 50, 1561-1573.
90. Liapakis, G.; Chan, W.C.; Papadokostaki, M., Javitch, J.A. Synergistic Contributions of the Functional Groups of Epinephrine to Its Affinity and Efficacy at the Beta2 Adrenergic Receptor. Mol. Pharmacol., 2004, 65, 1181-1190.
91. Roth, B.L.; Lopez, E.; Patel, S., Kroeze, W.K. The Multiplicity of Serotonin Receptors: Uselessly Diverse Molecules or an Embarrassment of Riches? Neuroscientist, 2000, 6, 252-262.
92. Fredholm, B.B.; AP, I.J.; Jacobson, K.A.; Linden, J., Muller, C.E. International Union of Basic and Clinical Pharmacology. Lxxxi. Nomenclature and Classification of Adenosine Receptors--an Update. Pharmacol. Rev., 2011, 63, 1-34.
93. Hawkins, P.C.D.; Skillman, A.G., Nicholls, A. Comparison of Shape-Matching and Docking as Virtual Screening Tools. J. Med. Chem., 2007, 50, 74-82.
94. Hann, M.M.; Leach, A.R., Harper, G. Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery. J. Chem. Inf. Comput. Sci., 2001, 41, 856-864.
95. Leach, A.R., Hann, M.M. Molecular Complexity and Fragment-Based Drug Discovery: Ten Years On. Curr. Opin. Chem. Biol., 2011, 15, 489-496.
96. Kitabgi, P. Targeting Neurotensin Receptors with Agonists and Antagonists for Therapeutic Purposes. Curr. Opin. Drug Discov. Devel., 2002, 5, 764-776.
97. Abbracchio, M.P.; Burnstock, G.; Boeynaems, J.M.; Barnard, E.A.; Boyer, J.L.; Kennedy, C.; Knight, G.E.; Fumagalli, M.; Gachet, C.; Jacobson, K.A., Weisman, G.A. International Union of Pharmacology Lviii: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy. Pharmacol. Rev., 2006, 58, 281-341.
98. Evers, A., Klabunde, T. Structure-Based Drug Discovery Using GPCR Homology Modeling: Successful Virtual Screening for Antagonists of the Alpha1a Adrenergic Receptor. J. Med. Chem., 2005, 48, 1088-1097.
99. Varady, J.; Wu, X.; Fang, X.; Min, J.; Hu, Z.; Levant, B., Wang, S. Molecular Modeling of the Three-Dimensional Structure of Dopamine 3 (D3) Subtype Receptor: Discovery of Novel and Potent D3 Ligands through a Hybrid Pharmacophore-and Structure-Based Database Searching Approach. J. Med. Chem., 2003, 46, 4377-4392.
100. 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.
101. Vilar, S.; Karpiak, J., Costanzi, S. Ligand and Structure-Based Models for the Prediction of Ligand-Receptor Affinities and Virtual Screenings: Development and Application to the Beta2-Adrenergic Receptor. J. Comput. Chem., 2010, 31, 707-720.
102. Kufareva, I.; Katritch, V.; Participants of GPCR Dock 2013. Stevens, R.C., Abagyan, R. Advances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment: Meeting New Challenges. Structure, 2014, 22, 1120-1139.
103. Michino, M.; Abola, E.; GPCR Dock 2008 participants; Brooks, C.L.; Dixon, J.S.; Moult, J., Stevens, R.C. Community-Wide Assessment of GPCR Structure Modelling and Ligand Docking: Gpcr Dock 2008. Nat. Rev. Drug Discovery, 2009, 8, 455-463.
104. Kufareva, I.; Rueda, M.; Katritch, V.; GPCR Dock 2010 participants; Stevens, R.C., Abagyan, R. Status of Gpcr Modeling and Docking as Reflected by Community-Wide GPCR Dock 2010 Assessment. Structure, 2011, 19, 1108-1126.
105. Katritch, V.; Rueda, M.; Lam, P.C.; Yeager, M., Abagyan, R. GPCR 3d Homology Models for Ligand Screening: Lessons Learned from Blind Predictions of Adenosine A2A Receptor Complex. Proteins: Struct., Funct., Bioinf., 2010, 78, 197-211.
106. Obiol-Pardo, C.; Lopez, L.; Pastor, M., Selent, J. Progress in the Structural Prediction of G Protein-Coupled Receptors: D3 Receptor in Complex with Eticlopride. Proteins: Struct., Funct., Bioinf., 2011, 79, 1695-1703.
107. Rodriguez, D.; Ranganathan, A., Carlsson, J. Strategies for Improved Modeling of GPCR-Drug Complexes: Blind Predictions of Serotonin Receptors Bound to Ergotamine. J. Chem. Inf. Model, 2014, 54, 2004-2021.
108. Sirci, F.; Istyastono, E.P.; Vischer, H.F.; Kooistra, A.J.; Nijmeijer, S.; Kuijer, M.; Wijtmans, M.; Mannhold, R.; Leurs, R.; de Esch, I.J.P., de Graaf, C. Virtual Fragment Screening: Discovery of Histamine H3 Receptor Ligands Using Ligand-Based and Protein-Based Molecular Fingerprints. J. Chem. Inf. Model, 2012, 52, 3308-3324.
109. Vass, M.; Schmidt, E.; Horti, F., Keseru, G.M. Virtual Fragment Screening on GPCRS: A Case Study on Dopamine D3 and Histamine H4 Receptors. Eur. J. Med. Chem., 2014, 77, 38-46.
110. Istyastono, E.P.; Kooistra, A.J.; Vischer, H.F.; Kuijer, M.; Roumen, L.; Nijmeijer, S.; Smits, R.A.; de Esch, I.J.P.; Leurs, R., de Graaf, C. Structure-Based Virtual Screening for Fragment-Like Ligands of the G Protein-Coupled Histamine H4 Receptor. Med. Chem. Commun., 2015, 6, 1003-1017.
111. Langmead, C.J.; Andrews, S.P.; Congreve, M.; Errey, J.C.; Hurrell, E.; Marshall, F.H.; Mason, J.S.; Richardson, C.M.; Robertson, N.; Zhukov, A., Weir, M. Identification of Novel Adenosine A(2A) Receptor Antagonists by Virtual Screening. J. Med. Chem., 2011, 55, 1904-1909.
112. Kolb, P.; Phan, K.; Gao, Z.G.; Marko, A.C.; Sali, A., Jacobson, K.A. Limits of Ligand Selectivity from Docking to Models: In Silico Screening for A(1) Adenosine Receptor Antagonists. PLoS One, 2012, 7, e49910.
113. Hajduk, P.J., Greer, J. A Decade of Fragment-Based Drug Design: Strategic Advances and Lessons Learned. Nat. Rev. Drug Discovery, 2007, 6, 211-219.
114. Baker, M. Fragment-Based Lead Discovery Grows Up. Nat. Rev. Drug Discovery, 2013, 12, 5-7.
115. Aristotelous, T.; Ahn, S.; Shukla, A.K.; Gawron, S.; Sassano, M.F.; Kahsai, A.W.; Wingler, L.M.; Zhu, X.; Tripathi-Shukla, P.; Huang, X.P.; Riley, J.; Besnard, J.; Read, K.D.; Roth, B.L.; Gilbert, I.H.; Hopkins, A.L.; Lefkowitz, R.J., Navratilova, I. Discovery of Beta2 Adrenergic Receptor Ligands Using Biosensor Fragment Screening of Tagged Wild-Type Receptor. ACS Med. Chem. Lett., 2013, 4, 1005-1010.
116. Congreve, M.; Rich, R.L.; Myszka, D.G.; Figaroa, F.; Siegal, G., Marshall, F.H. Fragment Screening of Stabilized G-Protein-Coupled Receptors Using Biophysical Methods. Methods Enzymol., 2011, 493, 115-136.
117. Stoddart, L.A.; Vernall, A.J.; Denman, J.L.; Briddon, S.J.; Kellam, B., Hill, S.J. Fragment Screening at Adenosine-A(3) Receptors in Living Cells Using a Fluorescence-Based Binding Assay. Chem. Biol., 2012, 19, 1105-1115.
118. Navratilova, I.; Besnard, J., Hopkins, A.L. Screening for GPCR Ligands Using Surface Plasmon Resonance. ACS Med. Chem. Lett., 2011, 2, 549-554.
119. Chen, D.; Errey, J.C.; Heitman, L.H.; Marshall, F.H.; Ijzerman, A.P., Siegal, G. Fragment Screening of GPCRS Using Biophysical Methods: Identification of Ligands of the Adenosine A(2A) Receptor with Novel Biological Activity. ACS Chem. Biol., 2012, 7, 2064-2073.
120. Murray, C.W., Blundell, T.L. Structural Biology in Fragment-Based Drug Design. Curr. Opin. Struct. Biol., 2010, 20, 497-507.
121. Andrews, S.P.; Brown, G.A., Christopher, J.A. Structure-Based and Fragment-Based GPCR Drug Discovery. ChemMedChem., 2014, 9, 256-275.
122. Korb, O.; Stutzle, T., Exner, T.E. Empirical Scoring Functions for Advanced Protein-Ligand Docking with Plants. J. Chem. Inf. Model, 2009, 49, 84-96.
123. Marcou, G., Rognan, D. Optimizing Fragment and Scaffold Docking by Use of Molecular Interaction Fingerprints. J. Chem. Inf. Model, 2007, 47, 195-207.
124. Chen, D.; Ranganathan, A.; IJzerman, A.P.; Siegal, G., Carlsson, J. Complementarity between in Silico and Biophysical Screening Approaches in Fragment-Based Lead Discovery against the A(2A) Adenosine Receptor. J. Chem. Inf. Model, 2013, 53, 2701-2714.
125. Sciabola, S.; Stanton, R.V.; Mills, J.E.; Flocco, M.M.; Baroni, M.; Cruciani, G.; Perruccio, F., Mason, J.S. High-Throughput Virtual Screening of Proteins Using Grid Molecular Interaction Fields. J. Chem. Inf. Model, 2010, 50, 155-169.
126. Christopher, J.A.; Brown, J.; Dore, A.S.; Errey, J.C.; Koglin, M.; Marshall, F.H.; Myszka, D.G.; Rich, R.L.; Tate, C.G.; Tehan, B.; Warne, T., Congreve, M. Biophysical Fragment Screening of the Beta1-Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design. J. Med. Chem., 2013, 56, 3446-3455.
127. Tosh, D.K.; Phan, K.; Gao, Z.G.; Gakh, A.A.; Xu, F.; Deflorian, F.; Abagyan, R.; Stevens, R.C.; Jacobson, K.A., Katritch, V. Optimization of Adenosine 5'-Carboxamide Derivatives as Adenosine Receptor Agonists Using Structure-Based Ligand Design and Fragment Screening. J. Med. Chem., 2012, 55, 4297-4308.
128. Vass, M.; Agai-Csongor, E.; Horti, F., Keseru, G.M. Multiple Fragment Docking and Linking in Primary and Secondary Pockets of Dopamine Receptors. ACS Med. Chem. Lett., 2014, 5, 1010-1014.
129. Sirci, F.; Goracci, L.; Rodriguez, D.; van Muijlwijk-Koezen, J.; Gutierrez-de-Teran, H., Mannhold, R. Ligand-, Structure-and Pharmacophore-Based Molecular Fingerprints: A Case Study on Adenosine A(1), A (2a), A (2b), and A (3) Receptor Antagonists. J. Comput.-Aided Mol. Des., 2012, 26, 1247-1266.
130. Shepherd, C.A.; Hopkins, A.L., Navratilova, I. Fragment Screening by Spr and Advanced Application to Gpcrs. Prog. Biophys. Mol. Biol., 2014, 116, 113-123.
131. Congreve, M.; Langmead, C.J.; Mason, J.S., Marshall, F.H. Progress in Structure Based Drug Design for G Protein-Coupled Receptors. J. Med. Chem., 2011, 54, 4283-4311.
132. Michino, M.; Beuming, T.; Donthamsetti, P.; Newman, A.H.; Javitch, J.A., Shi, L. What Can Crystal Structures of Aminergic Receptors Tell Us About Designing Subtype-Selective Ligands? Pharmacol. Rev., 2015, 67, 198-213.
133. Besnard, J.; Ruda, G.F.; Setola, V.; Abecassis, K.; Rodriguiz, R.M.; Huang, X.P.; Norval, S.; Sassano, M.F.; Shin, A.I.; Webster, L.A.; Simeons, F.R.; Stojanovski, L.; Prat, A.; Seidah, N.G.; Constam, D.B.; Bickerton, G.R.; Read, K.D.; Wetsel, W.C.; Gilbert, I.H.; Roth, B.L., Hopkins, A.L. Automated Design of Ligands to Polypharmacological Profiles. Nature, 2012, 492, 215-220.
134. Reutlinger, M.; Rodrigues, T.; Schneider, P., Schneider, G. Multi-Objective Molecular De Novo Design by Adaptive Fragment Prioritization. Angew. Chem. Int. Ed. Engl., 2014, 53, 4244-4248.
135. 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.
136. Dhawan, B.N.; Cesselin, F.; Raghubir, R.; Reisine, T.; Bradley, P.B.; Portoghese, P.S., Hamon, M. International Union of Pharmacology. Xii. Classification of Opioid Receptors. Pharmacol. Rev., 1996, 48, 567-592.
137. Gallantine, E.L., Meert, T.F. A Comparison of the Antinociceptive and Adverse Effects of the Mu-Opioid Agonist Morphine and the Delta-Opioid Agonist Snc80. Basic Clin. Pharmacol. Toxicol, 2005, 97, 39-51.
138. Kruse, A.C.; Kobilka, B.K.; Gautam, D.; Sexton, P.M.; Christopoulos, A., Wess, J. Muscarinic Acetylcholine Receptors: Novel Opportunities for Drug Development. Nat. Rev. Drug Discovery, 2014, 13, 549-560.
139. Hoyer, D.; Clarke, D.E.; Fozard, J.R.; Hartig, P.R.; Martin, G.R.; Mylecharane, E.J.; Saxena, P.R., Humphrey, P.P. International Union of Pharmacology Classification of Receptors for 5-Hydroxytryptamine (Serotonin). Pharmacol. Rev., 1994, 46, 157-203.
140. Berger, M.; Gray, J.A., Roth, B.L. The Expanded Biology of Serotonin. Annu. Rev. Med., 2009, 60, 355-366.
141. Katritch, V.; Kufareva, I., Abagyan, R. Structure Based Prediction of Subtype-Selectivity for Adenosine Receptor Antagonists. Neuropharmacology, 2011, 60, 108-115.
142. Paoletta, S.; Tosh, D.K.; Salvemini, D., Jacobson, K.A. Structural Probing of Off-Target G Protein-Coupled Receptor Activities within a Series of Adenosine/Adenine Congeners. PLoS One, 2014, 9, e97858.
143. Anighoro, A.; Bajorath, J., Rastelli, G. Polypharmacology: Challenges and Opportunities in Drug Discovery. J. Med. Chem., 2014, 57, 7874-7887.
144. Strachan, R.T.; Ferrara, G., Roth, B.L. Screening the Receptorome: An Efficient Approach for Drug Discovery and Target Validation. Drug Discov. Today, 2006, 11, 708-716.
145. Kohler, R.E.; Comerford, I.; Townley, S.; Haylock-Jacobs, S.; Clark-Lewis, I., McColl, S.R. Antagonism of the Chemokine Receptors CXCR3 and CXCR4 Reduces the Pathology of Experimental Autoimmune Encephalomyelitis. Brain Pathol, 2008, 18, 504-516.
146. Murakami, T.; Kawada, K.; Iwamoto, M.; Akagami, M.; Hida, K.; Nakanishi, Y.; Kanda, K.; Kawada, M.; Seno, H.; Taketo, M.M., Sakai, Y. The Role of CXCR3 and CXCR4 in Colorectal Cancer Metastasis. Int. J. Cancer, 2013, 132, 276-287.
147. Selent, J.; Lopez, L.; Sanz, F., Pastor, M. Multi-Receptor Binding Profile of Clozapine and Olanzapine: A Structural Study Based on the New Beta2 Adrenergic Receptor Template. ChemMedChem., 2008, 3, 1194-1198.
148. Selent, J.; Bauer-Mehren, A.; Lopez, L.; Loza, M.I.; Sanz, F., Pastor, M. A Novel Multilevel Statistical Method for the Study of the Relationships between Multireceptorial Binding Affinity Profiles and in vivo Endpoints. Mol. Pharmacol., 2010, 77, 149-158.
149. Stossel, A.; Schlenk, M.; Hinz, S.; Kuppers, P.; Heer, J.; Gutschow, M., Muller, C.E. Dual Targeting of Adenosine A(2A) Receptors and Monoamine Oxidase B by 4h-3,1-Benzothiazin-4-Ones. J. Med. Chem., 2013, 56, 4580-4596.
150. Christopoulos, A.; Changeux, J.P.; Catterall, W.A.; Fabbro, D.; Burris, T.P.; Cidlowski, J.A.; Olsen, R.W.; Peters, J.A.; Neubig, R.R.; Pin, J.P.; Sexton, P.M.; Kenakin, T.P.; Ehlert, F.J.; Spedding, M., Langmead, C.J. International Union of Basic and Clinical Pharmacology. Xc. Multisite Pharmacology: Recommendations for the Nomenclature of Receptor Allosterism and Allosteric Ligands. Pharmacol. Rev., 2014, 66, 918-947.
151. Lane, J.R.; Chubukov, P.; Liu, W.; Canals, M.; Cherezov, V.; Abagyan, R.; Stevens, R.C., Katritch, V. Structure-Based Ligand Discovery Targeting Orthosteric and Allosteric Pockets of Dopamine Receptors. Mol. Pharmacol., 2013, 84, 794-807.
152. Katritch, V.; Fenalti, G.; Abola, E.E.; Roth, B.L.; Cherezov, V., Stevens, R.C. Allosteric Sodium in Class a GPCR Signaling. Trends Biochem. Sci., 2014, 39, 233-244.
153. Selent, J.; Sanz, F.; Pastor, M., De Fabritiis, G. Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors. PLoS Comput. Biol., 2010, 6, e1000884.
154. Shang, Y.; LeRouzic, V.; Schneider, S.; Bisignano, P.; Pasternak, G.W., Filizola, M. Mechanistic Insights into the Allosteric Modulation of Opioid Receptors by Sodium Ions. Biochemistry, 2014, 53, 5140-5149.
155. Ranganathan, A.; Dror, R.O., Carlsson, J. Insights into the Role of Asp79(2.50) in Beta2 Adrenergic Receptor Activation from Molecular Dynamics Simulations. Biochemistry, 2014, 53, 7283-7296.
156. Massink, A.; Gutierrez-de-Teran, H.; Lenselink, E.B.; Ortiz Zacarias, N.V.; Xia, L.; Heitman, L.H.; Katritch, V.; Stevens, R.C., IJzerman, A.P. Sodium Ion Binding Pocket Mutations and Adenosine A2A Receptor Function. Mol. Pharmacol, 2015, 87, 305-313.
157. Gutierrez-de-Teran, H.; Massink, A.; Rodriguez, D.; Liu, W.; Han, G.W.; Joseph, J.S.; Katritch, I.; Heitman, L.H.; Xia, L.; IJzerman, A.P.; Cherezov, V.; Katritch, V., Stevens, R.C. The Role of a Sodium Ion Binding Site in the Allosteric Modulation of the A(2A) Adenosine G Protein-Coupled Receptor. Structure, 2013, 21, 2175-2185.
158. Livingston, K.E., Traynor, J.R. Disruption of the Na+ Ion Binding Site as a Mechanism for Positive Allosteric Modulation of the Mu-Opioid Receptor. Proc. Natl. Acad. Sci. USA. 2014, 111, 18369-18374.
159. Kennedy, D.P.; McRobb, F.M.; Leonhardt, S.A.; Purdy, M.; Figler, H.; Marshall, M.A.; Chordia, M.; Figler, R.; Linden, J.; Abagyan, R., Yeager, M. The Second Extracellular Loop of the Adenosine A1 Receptor Mediates Activity of Allosteric Enhancers. Mol. Pharmacol. 2014, 85, 301-309.
160. 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.
161. Sousa, S.F.; Fernandes, P.A., Ramos, M.J. Protein-Ligand Docking: Current Status and Future Challenges. Proteins: Struct., Funct., Bioinf. 2006, 65, 15-26.