Elucidation of conformational states, dynamics, and mechanism of binding in human κ-opioid receptor complexes

Journal of Chemical Information and Modeling

Volumn 54, Issue 8, 2014, Pages 2294-2308

  Leonis, Georgios ^a   Avramopoulos, Aggelos ^a   Salmas, Ramin Ekhteiari ^b   Durdagi, Serdar ^c   Yurtsever, Mine ^b   Papadopoulos, Manthos G ^a  

^a INSTITUTE OF BIOLOGY   (Greece)

^b ISTANBUL TECHNICAL UNIVERSITY   (Turkey)

^c BAHCESEHIR UNIVERSITY   (Turkey)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING ENERGY; CALCULATIONS; CONFORMATIONS; CRYSTAL STRUCTURE; FREE ENERGY; HYDROGEN BONDS; LIGANDS; LIPID BILAYERS; MOLECULAR DYNAMICS;

AB INITIO CALCULATIONS; CONFORMATIONAL DYNAMICS; ELECTROSTATIC CONTRIBUTIONS; G PROTEIN COUPLED RECEPTORS; HYDROGEN BOND INTERACTION; INTRAMOLECULAR INTERACTIONS; PHARMACOLOGICAL PROPERTIES; STRUCTURAL REARRANGEMENT;

COMPLEXATION;

7-HYDROXY-N-(1-((4-(3-HYDROXYPHENYL)-3,4-DIMETHYL-1-PIPERIDINYL)METHYL)-2-METHYLPROPYL)-1,2,3,4-TETRAHYDRO-3-ISOQUINOLINECARBOXAMIDE; CLERODANE DERIVATIVE; KAPPA OPIATE RECEPTOR; LIGAND; NARCOTIC ANALGESIC AGENT; NARCOTIC ANTAGONIST; PIPERIDINE DERIVATIVE; PROTEIN BINDING; SALVINORIN A; TETRAHYDROISOQUINOLINE DERIVATIVE;

BINDING SITE; CHEMISTRY; HUMAN; MOLECULAR DYNAMICS; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; STATIC ELECTRICITY; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS;

ANALGESICS, OPIOID; BINDING SITES; DITERPENES, CLERODANE; HUMANS; LIGANDS; MOLECULAR DYNAMICS SIMULATION; NARCOTIC ANTAGONISTS; PIPERIDINES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, OPIOID, KAPPA; STATIC ELECTRICITY; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROISOQUINOLINES; THERMODYNAMICS;

EID: 84906551636     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci5002873     Document Type: Article

References (82)

1. Kolb, P.; Klebe, G. The golden age of GPCR structural biology: any impact on drug design? Angew. Chem., Int. Ed. Engl. 2011, 50, 11573-11575
2. Stevens, R. C.; Cherezov, V.; Katritch, V.; Abagyan, R.; Kuhn, P.; Rosen, H.; Wuthrich, K. The GPCR Network: a large-scale collaboration to determine human GPCR structure and function Nat. Rev. Drug Discovery 2013, 12, 25-34
3. Hausch, F.; Holsboer, F. The seven pillars of molecular pharmacology: GPCR research honored with Nobel Prize for chemistry Angew. Chem., Int. Ed. Engl. 2012, 51, 12172-12175
4. Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.; Weis, W. I.; Kobilka, B. K.; Stevens, R. C. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor Science 2007, 318, 1258-1265
5. Chien, E. Y.; 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
6. Jaakola, V. P.; Griffith, M. T.; Hanson, M. A.; Cherezov, V.; Chien, E. Y.; 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
7. 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
8. 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
9. 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 micro-opioid receptor bound to a morphinan antagonist Nature 2012, 485, 321-326
10. 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
11. 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
12. 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
13. 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
14. 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
15. Waldhoer, M.; Bartlett, S. E.; Whistler, J. L. Opioid receptors Annu. Rev. Biochem. 2004, 73, 953-990
16. Carlezon, W. A., Jr.; Beguin, C.; Knoll, A. T.; Cohen, B. M. Kappa-opioid ligands in the study and treatment of mood disorders Pharmacol. Ther. 2009, 123, 334-343
17. Roth, B. L.; Baner, K.; Westkaemper, R.; Siebert, D.; Rice, K. C.; Steinberg, S.; Ernsberger, P.; Rothman, R. B. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 11934-11939
18. Yan, F.; Bikbulatov, R. V.; Mocanu, V.; Dicheva, N.; Parker, C. E.; Wetsel, W. C.; Mosier, P. D.; Westkaemper, R. B.; Allen, J. A.; Zjawiony, J. K.; Roth, B. L. Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor Biochemistry 2009, 48, 6898-6908
19. Carroll, I.; Thomas, J. B.; Dykstra, L. A.; Granger, A. L.; Allen, R. M.; Howard, J. L.; Pollard, G. T.; Aceto, M. D.; Harris, L. S. Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist Eur. J. Pharmacol. 2004, 501, 111-119
20. Thomas, J. B.; Atkinson, R. N.; Rothman, R. B.; Fix, S. E.; Mascarella, S. W.; Vinson, N. A.; Xu, H.; Dersch, C. M.; Lu, Y.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. Identification of the first trans-(3R,4R)-dimethyl-4-(3- hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity J. Med. Chem. 2001, 44, 2687-2690
21. Dror, R. O.; Pan, A. C.; Arlow, D. H.; Borhani, D. W.; Maragakis, P.; Shan, Y.; Xu, H.; Shaw, D. E. Pathway and mechanism of drug binding to G-protein-coupled receptors Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 13118-13123
22. Heifetz, A.; Morris, G. B.; Biggin, P. C.; Barker, O.; Fryatt, T.; Bentley, J.; Hallett, D.; Manikowski, D.; Pal, S.; Reifegerste, R.; Slack, M.; Law, R. Study of human Orexin-1 and -2 G-protein-coupled receptors with novel and published antagonists by modeling, molecular dynamics simulations, and site-directed mutagenesis Biochemistry 2012, 51, 3178-3197
23. Provasi, D.; Artacho, M. C.; Negri, A.; Mobarec, J. C.; Filizola, M. Ligand-induced modulation of the free-energy landscape of G protein-coupled receptors explored by adaptive biasing techniques PLoS Comput. Biol. 2011, 7, e1002193
24. Provasi, D.; Filizola, M. Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics Biophys. J. 2010, 98, 2347-2355
25. Provasi, D.; Bortolato, A.; Filizola, M. Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics Biochemistry 2009, 48, 10020-10029
26. 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
27. Deflorian, F.; Kumar, T. S.; Phan, K.; Gao, Z. G.; Xu, F.; Wu, H.; Katritch, V.; Stevens, R. C.; Jacobson, K. A. Evaluation of molecular modeling of agonist binding in light of the crystallographic structure of an agonist-bound A(2)A adenosine receptor J. Med. Chem. 2012, 55, 538-552
28. McGovern, D. L.; Mosier, P. D.; Roth, B. L.; Westkaemper, R. B. CoMFA analyses of C-2 position salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity J. Mol. Graphics Modell. 2010, 28, 612-625
29. Perez, D. M.; Karnik, S. S. Multiple signaling states of G-protein-coupled receptors Pharmacol Rev. 2005, 57, 147-161
30. 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
31. Fiser, A.; Do, R. K.; Sali, A. Modeling of loops in protein structures Protein Sci. 2000, 9, 1753-1773
32. Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints J. Mol. Biol. 1993, 234, 779-815
33. Krivov, G. G.; Shapovalov, M. V.; Dunbrack, R. L., Jr. Improved prediction of protein side-chain conformations with SCWRL4 Proteins 2009, 77, 778-795
34. Case, D. A.; Cheatham, T. E., 3rd; Darden, T.; Gohlke, H.; Luo, R.; Merz, K. M., Jr.; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R. J. The Amber biomolecular simulation programs J. Comput. Chem. 2005, 26, 1668-1688
35. Case, D. A.; Darden, T. A.; Cheatham, T. E., III; Simmerling, C.; Wang, J.; Duke, R. E.; Luo, R.; Walker, R. C.; Zhang, W.; Merz, K. M.; Roberts, B. P.; Wang, B.; Hayik, S.; Roitberg, A.; Seabra, G.; Kolossvary, I.; Wong, K. F.; Paesani, F.; Vanicek, J.; Liu, J.; Wu, X.; Brozell, S. R.; Steinbrecher, T.; Gohlke, H.; Cai, Q.; Ye, X.; Wang, J.; Hsieh, M. J.; Cui, G.; Roe, D. R.; Mathews, D. H.; Seetin, M. G.; Sagui, C.; Babin, V.; Luchko, T.; Gusarov, S.; Kovalenko, A.; Kollman, P. A. AMBER 11; University of California: San Francisco, CA, 2010.
36. Hooft, R. W.; Vriend, G.; Sander, C.; Abola, E. E. Errors in protein structures Nature 1996, 381, 272
37. Vriend, G. WHAT IF: a molecular modeling and drug design program J. Mol. Graphics 1990, 8, 52-56
38. Bas, D. C.; Rogers, D. M.; Jensen, J. H. Very fast prediction and rationalization of pKa values for protein-ligand complexes Proteins 2008, 73, 765-783
39. Li, H.; Robertson, A. D.; Jensen, J. H. Very fast empirical prediction and rationalization of protein pKa values Proteins 2005, 61, 704-721
40. Dolinsky, T. J.; Nielsen, J. E.; McCammon, J. A.; Baker, N. A. PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations Nucleic Acids Res. 2004, 32, W665-W667
41. Katritch, V. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Personal communication, La Jolla, CA, May 2012.
42. Hornak, V.; Abel, R.; Okur, A.; Strockbine, B.; Roitberg, A.; Simmerling, C. Comparison of multiple Amber force fields and development of improved protein backbone parameters Proteins 2006, 65, 712-725
43. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera - a visualization system for exploratory research and analysis J. Comput. Chem. 2004, 25, 1605-1612
44. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. In Revision A; Gaussian, Inc.: Wallingford, CT, 2009.
45. Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general amber force field J. Comput. Chem. 2004, 25, 1157-1174
46. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of Simple Potential Functions for Simulating Liquid Water J. Chem. Phys. 1983, 79, 926-935
47. Darden, T.; York, D.; Pedersen, L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems J. Chem. Phys. 1993, 98, 10089-10092
48. Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes J. Comput. Phys. 1977, 23, 327-341
49. Izaguirre, J. A.; Catarello, D. P.; Wozniak, J. M.; Skeel, R. D. Langevin stabilization of molecular dynamics J. Chem. Phys. 2001, 114, 2090-2098
50. Simmerling, C.; Elber, R.; Zhang, J. Moil-view-A program for visualization of structure and dynamics of biomolecules and STO-A program for computing stochastic paths. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, Modelling of Biomolecular Structures and Mechanisms, Pullman, A.; Jortner, J., Eds.; Springer: Jerusalem, Israel, 1995;, 27, pp 241-265.
51. Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R. D.; Kale, L.; Schulten, K. Scalable molecular dynamics with NAMD J. Comput. Chem. 2005, 26, 1781-1802
52. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., 3rd Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models Acc. Chem. Res. 2000, 33, 889-897
53. Gohlke, H.; Kiel, C.; Case, D. A. Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras-RalGDS complexes J. Mol. Biol. 2003, 330, 891-913
54. Wang, W.; Kollman, P. A. Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 14937-14942
55. Xu, Y.; Wang, R. A computational analysis of the binding affinities of FKBP12 inhibitors using the MM-PB/SA method Proteins 2006, 64, 1058-1068
56. Honig, B.; Nicholls, A. Classical electrostatics in biology and chemistry Science 1995, 268, 1144-1149
57. Weiser, J.; Shenkin, P. S.; Still, W. C. Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO) J. Comput. Chem. 1999, 20, 217-230
58. Hou, T.; Wang, J.; Li, Y.; Wang, W. Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations J. Chem. Inf. Model. 2011, 51, 69-82
59. Miller, B. R., 3rd; McGee, T. D., Jr.; Swails, J. M.; Homeyer, N.; Gohlke, H.; Roitberg, A. E. MMPBSA.py: An Efficient Program for End-State Free Energy Calculations J. Chem. Theory Comput. 2012, 8, 3314-3321
60. Su, P.; Li, H. Energy decomposition analysis of covalent bonds and intermolecular interactions J. Chem. Phys. 2009, 131, 014102
61. Boys, S. F.; Bernardi, F. Calculation of Small Molecular Interactions by Differences of Separate Total Energies-Some Procedures with Reduced Errors Mol. Phys. 1970, 19, 553-566
62. Schmidt, M. W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M. S.; Jensen, J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K. A.; Su, S. J.; Windus, T. L.; Dupuis, M.; Montgomery, J. A. General Atomic and Molecular Electronic-Structure System J. Comput. Chem. 1993, 14, 1347-1363
63. Bader, R. F. W. Atoms in Molecules: A Quantum Theory; Clarendon: Oxford: 1990.
64. Bader, R. F. W. A bond path: A universal indicator of bonded interactions J. Phys. Chem. A 1998, 102, 7314-7323
65. Grabowski, S. J. Hydrogen bonding strength-measures based on geometric and topological parameters J. Phys. Org. Chem. 2004, 17, 18-31
66. Espinosa, E.; Molins, E.; Lecomte, C. Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities Chem. Phys. Lett. 1998, 285, 170-173
67. Biegler-Konig, F.; Schonbohm, J. Update of the AIM2000-program for atoms in molecules J. Comput. Chem. 2002, 23, 1489-1494
68. Collu, F.; Ceccarelli, M.; Ruggerone, P. Exploring binding properties of agonists interacting with a delta-opioid receptor PLoS One 2012, 7, e52633
69. Kukic, P.; Nielsen, J. E. Electrostatics in proteins and protein-ligand complexes Future Med. Chem. 2010, 2, 647-666
70. Leonis, G.; Steinbrecher, T.; Papadopoulos, M. G. A contribution to the drug resistance mechanism of darunavir, amprenavir, indinavir, and saquinavir complexes with HIV-1 protease due to flap mutation I50V: a systematic MM-PBSA and thermodynamic integration study J. Chem. Inf. Model. 2013, 53, 2141-2153
71. Politi, A.; Leonis, G.; Tzoupis, H.; Ntountaniotis, D.; Papadopoulos, M. G.; Grdadolnik, S. G.; Mavromoustakos, T. Conformational Properties and Energetic Analysis of Aliskiren in Solution and Receptor Site Mol. Inf. 2011, 30, 973-985
72. Tzoupis, H.; Leonis, G.; Durdagi, S.; Mouchlis, V.; Mavromoustakos, T.; Papadopoulos, M. G. Binding of novel fullerene inhibitors to HIV-1 protease: insight through molecular dynamics and molecular mechanics Poisson-Boltzmann surface area calculations J. Comput.-Aided Mol. Des 2011, 25, 959-976
73. Tzoupis, H.; Leonis, G.; Megariotis, G.; Supuran, C. T.; Mavromoustakos, T.; Papadopoulos, M. G. Dual inhibitors for aspartic proteases HIV-1 PR and renin: advancements in AIDS-hypertension-diabetes linkage via molecular dynamics, inhibition assays, and binding free energy calculations J. Med. Chem. 2012, 55, 5784-5796
74. Gouda, H.; Kuntz, I. D.; Case, D. A.; Kollman, P. A. Free energy calculations for theophylline binding to an RNA aptamer: Comparison of MM-PBSA and thermodynamic integration methods Biopolymers 2003, 68, 16-34
75. Runyon, S. P.; Brieaddy, L. E.; Mascarella, S. W.; Thomas, J. B.; Navarro, H. A.; Howard, J. L.; Pollard, G. T.; Carroll, F. I. Analogues of (3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1- piperidinyl ]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3- isoquinolinecarboxamide (JDTic). Synthesis and in vitro and in vivo opioid receptor antagonist activity J. Med. Chem. 2010, 53, 5290-5301
76. Kane, B. E.; Nieto, M. J.; McCurdy, C. R.; Ferguson, D. M. A unique binding epitope for salvinorin A, a non-nitrogenous kappa opioid receptor agonist FEBS J. 2006, 273, 1966-1974
77. Vortherms, T. A.; Mosier, P. D.; Westkaemper, R. B.; Roth, B. L. Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity. Studies with salvinorin A and the kappa-opioid receptor J. Biol. Chem. 2007, 282, 3146-3156
78. Yan, F.; Mosier, P. D.; Westkaemper, R. B.; Roth, B. L. Galpha-subunits differentially alter the conformation and agonist affinity of kappa-opioid receptors Biochemistry 2008, 47, 1567-1578
79. Yan, F.; Mosier, P. D.; Westkaemper, R. B.; Stewart, J.; Zjawiony, J. K.; Vortherms, T. A.; Sheffler, D. J.; Roth, B. L. Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors Biochemistry 2005, 44, 8643-8651
80. Jo, S.; Kim, T.; Iyer, V. G.; Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM J. Comput. Chem. 2008, 29, 1859-1865
81. Jo, S.; Lim, J. B.; Klauda, J. B.; Im, W. CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes Biophys. J. 2009, 97, 50-58
82. Orientations of Proteins in Membranes (OPM) database. http://opm.phar.umich.edu (accessed June 27, 2014).