Molecular dynamics simulations of the adenosine A2a receptor: Structural stability, sampling, and convergence

Journal of Chemical Information and Modeling

Volumn 53, Issue 5, 2013, Pages 1168-1178

  Ng, Hui Wen ^a   Laughton, Charles A ^b   Doughty, Stephen W ^a  

^a UNIVERSITY OF NOTTINGHAM MALAYSIA CAMPUS   (Malaysia)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LIGANDS; PROTEINS; STABILITY;

ACCURATE PREDICTION; ADENOSINE RECEPTOR; CONFORMATIONAL DYNAMICS; G PROTEIN COUPLED RECEPTORS; MOLECULAR DYNAMICS SIMULATIONS; MOLECULAR SIMULATIONS; RELIABILITY AND ROBUSTNESS; STRUCTURAL STABILITIES;

MOLECULAR DYNAMICS;

ADENOSINE A2A RECEPTOR; APOPROTEIN; LIGAND;

ARTICLE; CELL MEMBRANE; CHEMISTRY; METABOLISM; MOLECULAR DYNAMICS; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY;

APOPROTEINS; CELL MEMBRANE; LIGANDS; MOLECULAR DYNAMICS SIMULATION; PROTEIN STABILITY; PROTEIN STRUCTURE, SECONDARY; RECEPTOR, ADENOSINE A2A;

EID: 84878171320     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci300610w     Document Type: Article

References (94)

1. Klotz, L.; Boccon-Gibod, L.; Shore, N. D.; Andreou, C.; Persson, B. E.; Cantor, P.; Jensen, J. K.; Olesen, T. K.; Schroder, F. H. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer BJU Int. 2008, 102, 1531-1538
2. Abel, S.; Russell, D.; Whitlock, L. A.; Ridgway, C. E.; Nedderman, A. N.; Walker, D. K. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects Br. J. Clin. Pharmacol. 2008, 65 (Suppl. 1) 60-67 (Pubitemid 351366540)
3. 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
4. Tyndall, J. D.; Pfeiffer, B.; Abbenante, G.; Fairlie, D. P. Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure Chem. Rev. 2005, 105, 793-826 (Pubitemid 40527376)
5. Gruber, C. W.; Muttenthaler, M.; Freissmuth, M. Ligand-based peptide design and combinatorial peptide libraries to target G protein-coupled receptors Curr. Pharm. Des. 2010, 16, 3071-3088
6. Nambi, P.; Aiyar, N. G protein-coupled receptors in drug discovery Assay Drug Dev. Technol. 2003, 1, 305-310
7. Drews, J. Drug discovery: a historical perspective Science 2000, 287, 1960-1964 (Pubitemid 30158662)
8. Vassilatis, D. K.; Hohmann, J. G.; Zeng, H.; Li, F.; Ranchalis, J. E.; Mortrud, M. T.; Brown, A.; Rodriguez, S. S.; Weller, J. R.; Wright, A. C.; Bergmann, J. E.; Gaitanaris, G. A. The G protein-coupled receptor repertoires of human and mouse Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 4903-4908 (Pubitemid 36457826)
9. Jacobson, K. A.; Gao, Z. G. Adenosine receptors as therapeutic targets Nat. Rev. Drug Discov. 2006, 5, 247-264 (Pubitemid 43336037)
10. Weiss, S. M.; Benwell, K.; Cliffe, I. A.; Gillespie, R. J.; Knight, A. R.; Lerpiniere, J.; Misra, A.; Pratt, R. M.; Revell, D.; Upton, R.; Dourish, C. T. Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease Neurology 2003, 61 (11 Suppl. 6) S101-106
11. Xu, K.; Bastia, E.; Schwarzschild, M. Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease Pharmacol. Ther. 2005, 105, 267-310 (Pubitemid 40297894)
12. Hauser, R. A.; Schwarzschild, M. A. Adenosine A2A receptor antagonists for Parkinson's disease: rationale, therapeutic potential and clinical experience Drugs Aging 2005, 22, 471-482 (Pubitemid 41003061)
13. Dong, Q.; Ginsberg, H. N.; Erlanger, B. F. Overexpression of the A1 adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance Diabetes Obes. Metab. 2001, 3, 360-366 (Pubitemid 33072216)
14. Baharav, E.; Bar-Yehuda, S.; Madi, L.; Silberman, D.; Rath-Wolfson, L.; Halpren, M.; Ochaion, A.; Weinberger, A.; Fishman, P. Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models J. Rheumatol. 2005, 32, 469-476 (Pubitemid 40381417)
15. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le Trong, I.; Teller, D. C.; Okada, T.; Stenkamp, R. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: A G protein-coupled receptor Science 2000, 289, 739-745 (Pubitemid 30650186)
16. Rasmussen, S. G.; Choi, H. J.; Rosenbaum, D. M.; Kobilka, T. S.; Thian, F. S.; Edwards, P. C.; Burghammer, M.; Ratnala, V. R.; Sanishvili, R.; Fischetti, R. F.; Schertler, G. F.; Weis, W. I.; Kobilka, B. K. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor Nature 2007, 450, 383-387 (Pubitemid 350126755)
17. Warne, W.; Serrano-Vega, M. J.; Baker, J. G.; Moukhametzianov, R.; Edwards, P. C.; Henderson, R. Structure of a beta1-adrenergic G-protein-coupled receptor Nature 2008, 454, 486-491
18. 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
19. 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
20. 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, 1091-5
21. 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 2012, 475, 65-70
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
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. Park, S. H.; Das, B. B.; Casagrande, F.; Tian, Y.; Nothnagel, H. J.; Chu, M.; Kiefer, H.; Maier, K.; De Angelis, A. A.; Marassi, F. M.; Opella, S. J. Structure of the chemokine receptor CXCR1 in phospholipid bilayers Nature 2012, 491, 779-783
30. 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
31. 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
32. Rodriguez, D.; Pineiro, A.; Gutierrez-de-Teran, H. Molecular Dynamics Simulations Reveal Insights into Key Structural Elements of Adenosine Receptors Biochemistry 2011, 50, 4194-4208
33. Filizola, M.; Wang, S. X.; Weinstein, H. Dynamic models of G-protein coupled receptor dimers: indications of asymmetry in the rhodopsin dimer from molecular dynamics simulations in a POPC bilayer J. Comput. Aided Mol. Des. 2006, 20, 405-16 (Pubitemid 44823879)
34. Rohrig, U. F.; Guidoni, L.; Rothlisberger, U. Early steps of the intramolecular signal transduction in rhodopsin explored by molecular dynamics simulations Biochemistry 2002, 41, 10799-809 (Pubitemid 34971057)
35. Ivanov, A. A.; Baskin, I. I.; Palyulin, V. A.; Piccagli, L.; Baraldi, P. G.; Zefirov, N. S. Molecular modeling and molecular dynamics simulation of the human A2B adenosine receptor. The study of the possible binding modes of the A2B receptor antagonists J. Med. Chem. 2005, 48, 6813-6820 (Pubitemid 41533103)
36. Arinaminpathy, Y.; Sansom, M. S.; Biggin, P. C. Molecular dynamics simulations of the ligand-binding domain of the ionotropic glutamate receptor GluR2 Biophys. J. 2002, 82, 676-683 (Pubitemid 34111209)
37. Kaye, S. L.; Sansom, M. S.; Biggin, P. C. Molecular dynamics simulations of the ligand-binding domain of an N-methyl-D-aspartate receptor J. Biol. Chem. 2006, 281, 12736-12742 (Pubitemid 43855364)
38. Hallmen, C.; Wiese, M. Molecular dynamics simulation of the human adenosine A3 receptor: agonist induced conformational changes of Trp243 J. Comput. Aided Mol. Des. 2006, 20, 673-684 (Pubitemid 46023929)
39. Crozier, P. S.; Stevens, M. J.; Forrest, L. R.; Woolf, T. B. Molecular dynamics simulation of dark-adapted rhodopsin in an explicit membrane bilayer: coupling between local retinal and larger scale conformational change J. Mol. Biol. 2003, 333, 493-514 (Pubitemid 37229077)
40. Chen, J. Z.; Wang, J.; Xie, X. Q. GPCR structure-based virtual screening approach for CB2 antagonist search J. Chem. Inf. Model. 2007, 47, 1626-1637 (Pubitemid 47210066)
41. Schlegel, B.; Laggner, C.; Meier, R.; Langer, T.; Schnell, D.; Seifert, R.; Stark, H.; Holtje, H. D.; Sippl, W. Generation of a homology model of the human histamine H(3) receptor for ligand docking and pharmacophore-based screening J. Comput. Aided Mol. Des. 2007, 21, 437-453 (Pubitemid 47423277)
42. Yarnitzky, T.; Levit, A.; Niv, M. Y. Homology modeling of G-protein-coupled receptors with X-ray structures on the rise Curr. Opin. Drug Discov. Dev. 2010, 13, 317-325
43. 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 2011, 79, 1695-1703
44. Amadei, A.; Linssen, A. B.; Berendsen, H. J. Essential dynamics of proteins Proteins 1993, 17, 412-425 (Pubitemid 23358549)
45. Clarage, J. B.; Romo, T.; Andrews, B. K.; Pettitt, B. M.; Phillips, G. N., Jr. A sampling problem in molecular dynamics simulations of macromolecules Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 3288-3292
46. Balsera, M. W., W.; Oono, Y.; Shculten, K. Principal Component Analysis and Long Time Protein Dynamics J. Phys. Chem. 1996, 100, 2567-2572 (Pubitemid 126793208)
47. Amadei, A.; Ceruso, M. A.; Di Nola, A. On the convergence of the conformational coordinates basis set obtained by the essential dynamics analysis of proteins' molecular dynamics simulations Proteins 1999, 36, 419-424 (Pubitemid 29387740)
48. Hess, B. Similarities between principal components of protein dynamics and random diffusion Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 2000, 62, 8438-8448 (Pubitemid 32087906)
49. Hess, B. Convergence of sampling in protein simulations Phys. Rev. E Stat. Nonlin. Soft Matter. Phys 2002, 65, 031910-031920
50. Faraldo-Gomez, J. D.; Forrest, L. R.; Baaden, M.; Bond, P. J.; Domene, C.; Patargias, G.; Cuthbertson, J.; Sansom, M. S. Conformational sampling and dynamics of membrane proteins from 10-ns computer simulations Proteins 2004, 57, 783-791 (Pubitemid 39626999)
51. Grossfield, A. S.; Feller, S. E.; Pitman, M. C. Convergence of Molecular Dynamics Simulations of Membrane Proteins Proteins 2007, 67, 31-40 (Pubitemid 46340124)
52. Romo, T. G. A. Block Covariance Overlap Method and Convergence in Molecular Dynamics Simulation J. Chem. Theory Comput. 2011, 7, 2464-2472
53. Romo, T. D.; Grossfield, A. Validating and improving elastic network models with molecular dynamics simulations Proteins 2011, 79, 23-34
54. SYBYL Biopolymer modelling manual, version 6.5; Tripos Inc.: St. Louis, MO, 1998; http://www.tripos.com.
55. Oostenbrink, C.; Villa, A.; Mark, A. E.; van Gunsteren, W. F. A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6 J. Comput. Chem. 2004, 25, 1656-1676
56. Berendsen, H. J. C.; van der Spoel, D. van drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation Comput. Phys. Commun. 1995, 91, 43-56
57. van der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A. E.; Berendsen, H. J. C. GROMACS: Fast, flexible, and free J. Comput. Chem. 2005, 26, 1701-1718 (Pubitemid 43076182)
58. Hess, B.; Kutzner, C.; van der spoel, D.; Lindahl, E. GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation J. Chem. Theory Comput. 2008, 4, 435-447
59. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: A program to check the stereochemical quality of protein structures J. Appl. Crystallogr. 1993, 26, 283-291
60. Vriend, G. WHAT IF: A molecular modeling and drug design program J. Mol. Graph. 1990, 8, 52-56 (Pubitemid 20717037)
61. Schuttelkopf, A. W.; van Aalten, D. M. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes Acta Crystallogr. D Biol. Crystallogr. 2004, 60, 1355-1363 (Pubitemid 41079731)
62. Lemkul, J. A.; Allen, W. J.; Bevan, D. R. Practical considerations for building GROMOS-compatible small-molecule topologies J. Chem. Inf. Model. 2010, 50, 2221-2235
63. Berger, O.; Edholm, O.; Jahnig, F. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature Biophys. J. 1997, 72, 2002-2013 (Pubitemid 27184429)
64. Wolf, M. G.; Hoefling, M.; Aponte-Santamaria, C.; Grubmuller, H.; Groenhof, G. g-membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation J. Comput. Chem. 2010, 31, 2169-2174
65. Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; Hermans, J. Interaction Models for Water in Relation to Protein Hydration. In In Intermolecular Forces; Pullman, B., Ed.; Reidel Publishing Company: Reidel, Dordrecht, The Netherlands, 1981; pp 331-342.
66. Essmann, U.; Perera, L.; Berkowitz, M. L. A smooth particle mesh Ewald method J. Chem. Phys. 1995, 103, 8577-8593
67. Hess, B.; Bekker, H.; Berendsen, H. J. C.; Fraaije, J. G. E. M. LINCS: A Linear Constraint Solver for Molecular Simulations J. Comput. Chem. 1997, 18, 1463-1472 (Pubitemid 127637344)
68. Bussi, G.; Donadio, D.; Parinello, M. Canonical sampling through velocity rescaling J. Chem. Phys. 2007, 126, 014101-014108
69. Parinello, M.; Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method J. Appl. Phys. 1981, 52, 7182-7190 (Pubitemid 12456820)
70. Williams, T.; Kelley, C. Gnuplot 4.5: an interactive plotting program; 2011.
71. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions Protein Eng. 1995, 8, 127-134
72. Haider, S.; Parkinson, G. N.; Neidle, S. Molecular dynamics and principal components analysis of human telomeric quadruplex multimers Biophys. J. 2008, 95, 296-311
73. Humphrey, W.; Dalke, A.; Schulten, K. VMD-Visual Molecular Dynamics J. Mol. Graph. 1996, 14, 33-38
74. 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 beta(2) adrenoceptor Nature 2011, 469, 175-180
75. 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
76. Li, J.; Edwards, P. C.; Burghammer, M.; Villa, C.; Schertler, G. F. Structure of bovine rhodopsin in a trigonal crystal form J. Mol. Biol. 2004, 343, 1409-1438 (Pubitemid 39387834)
77. Park, J. H.; Scheerer, P.; Hofmann, K. P.; Choe, H. W.; Ernst, O. P. Crystal structure of the ligand-free G-protein-coupled receptor opsin Nature 2008, 454, 183-187 (Pubitemid 351969893)
78. 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, 322-327
79. 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
80. Lyman, E.; Zuckerman, D. M. On the structural convergence of biomolecular simulations by determination of the effective sample size J. Phys. Chem. B 2007, 111, 12876-12882 (Pubitemid 350136478)
81. Grossfield, A.; Zuckerman, D. M. Quantifying uncertainty and sampling quality in biomolecular simulations Annu. Rep. Comput. Chem. 2009, 5, 23-48
82. Myburgh, D. B.; Millar, R. P.; Hapgood, J. P. Alanine-261 in intracellular loop III of the human gonadotropin-releasing hormone receptor is crucial for G-protein coupling and receptor internalization Biochem. J. 1998, 331 (Pt 3) 893-896 (Pubitemid 28211914)
83. Schulz, A.; Schoneberg, T.; Paschke, R.; Schultz, G.; Gudermann, T. Role of the third intracellular loop for the activation of gonadotropin receptors Mol. Endocrinol. 1999, 13, 181-190 (Pubitemid 29067994)
84. Angelova, K.; Fanelli, F.; Puett, D. Contributions of intracellular loops 2 and 3 of the lutropin receptor in Gs coupling Mol. Endocrinol. 2008, 22, 126-38
85. Deupi, X.; Li, X. D.; Schertler, G. F. Ligands stabilize specific GPCR conformations: but how? Structure 2012, 20, 1289-1290
86. Dore, A. S.; Robertson, N.; Errey, J. C.; Ng, I.; Hollenstein, K.; Tehan, B.; Hurrell, E.; Bennett, K.; Congreve, M.; Magnani, F.; Tate, C. G.; Weir, M.; Marshall, F. H. Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine Structure 2012, 19, 1283-1293
87. Liu, W.; Chun, E.; Thompson, A. A.; Chubukov, P.; Xu, F.; Katritch, V.; Han, G. W.; Roth, C. B.; Heitman, L. H.; AP, I. J.; Cherezov, V.; Stevens, R. C. Structural basis for allosteric regulation of GPCRs by sodium ions Science 2012, 337, 232-236
88. Hino, T.; Arakawa, T.; Iwanari, H.; Yurugi-Kobayashi, T.; Ikeda-Suno, C.; Nakada-Nakura, Y.; Kusano-Arai, O.; Weyand, S.; Shimamura, T.; Nomura, N.; Cameron, A. D.; Kobayashi, T.; Hamakubo, T.; Iwata, S.; Murata, T. G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody Nature 2012, 482, 237-240
89. Congreve, M.; Andrews, S. P.; Dore, A. S.; Hollenstein, K.; Hurrell, E.; Langmead, C. J.; Mason, J. S.; Ng, I. W.; Tehan, B.; Zhukov, A.; Weir, M.; Marshall, F. H. Discovery of 1,2,4-triazine derivatives as adenosine A(2A) antagonists using structure based drug design J. Med. Chem. 2012, 55, 1898-1903
90. Ballesteros, J. A.; Jensen, A. D.; Liapakis, G.; Rasmussen, S. G.; Shi, L.; Gether, U.; Javitch, J. A. Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6 J. Biol. Chem. 2001, 276, 29171-29177
91. Shi, L.; Liapakis, G.; Xu, R.; Guarnieri, F.; Ballesteros, J. A.; Javitch, J. A. Beta2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch J. Biol. Chem. 2002, 277, 40989-40996 (Pubitemid 35215688)
92. Konopka, J. B.; Margarit, S. M.; Dube, P. Mutation of Pro-258 in transmembrane domain 6 constitutively activates the G protein-coupled alpha-factor receptor Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 6764-6769 (Pubitemid 26230384)
93. Kim, S.-K.; Riley, L.; Abrol, R.; Jacobson, K. A.; Goddard, W. A. Predicted structures of agonist and antagonist bound complexes of adenosine A3 receptor Proteins 2011, 79, 1878-1897
94. Dror, R. O.; Arlow, D. H.; Maragakis, P.; Mildorf, T. J.; Pan, A. C.; Xu, H.; Borhani, D. W.; Shaw, D. E. Activation mechanism of the beta2-adrenergic receptor Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 18684-18689