PREDICT modeling and in-silico screening for G-protein coupled receptors

Proteins: Structure, Function and Genetics

Volumn 57, Issue 1, 2004, Pages 51-86

  Shacham, Sharon ^a   Marantz, Yael ^a   Bar Haim, Shay ^a   Kalid, Ori ^a   Warshaviak, Dora ^a   Avisar, Noa ^a   Inbal, Boaz ^a   Heifetz, Alexander ^a   Fichman, Merav ^a   Topf, Maya ^a,b   Naor, Zvi ^a,c   Noiman, Silvia ^a   Becker, Oren M ^a  

^a Predix Pharmaceuticals Ltd   (Israel)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c TEL AVIV UNIVERSITY   (Israel)

Author keywords

Docking; GPCR; In silico screening; Modeling; Structure based drug discovery

Indexed keywords

DOPAMINE 2 RECEPTOR; G PROTEIN COUPLED RECEPTOR; NEUROPEPTIDE Y RECEPTOR; NEUROPEPTIDE Y1 RECEPTOR; SILICON; TACHYKININ RECEPTOR;

ALGORITHM; ALPHA HELIX; ARTICLE; COMPLEX FORMATION; CRYSTAL STRUCTURE; MODEL; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN STRUCTURE; SCREENING; STRUCTURE ANALYSIS; X RAY CRYSTALLOGRAPHY;

ALGORITHMS; AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; COMBINATORIAL CHEMISTRY TECHNIQUES; COMPUTER SIMULATION; DRUG DESIGN; HUMANS; HYDROPHOBICITY; LIGANDS; MODELS, CHEMICAL; MODELS, MOLECULAR; MONTE CARLO METHOD; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, DOPAMINE D2; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROKININ-1; RECEPTORS, NEUROPEPTIDE Y; RHODOPSIN; STEREOISOMERISM; THERMODYNAMICS;

EID: 4444274752     PISSN: 08873585     EISSN: None     Source Type: Journal    
DOI: 10.1002/prot.20195     Document Type: Article

References (187)

1. Gether U. Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 2000;21:90-113.
2. Drews J. Drug discovery: a historical perspective. Science 2000;287:1960-1964.
3. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Migano M. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000;289:739-745.
4. Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM. X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases. Science 1997;277:1676-1681.
5. Becker OM, Shacham S, Marantz Y, Noiman S. Modeling the 3D structure of GPCRs: advances and application to drug discovery. Curr Opin Drug Discov Dev 2003;6:353-361.
6. Bissantz C, Bernard P, Hibert M, Rognan D. Protein-based virtual screening of chemical databases. II. Are homology models of G-protein coupled receptors suitable targets? Proteins 2003;50:5-25.
7. John B, Sali A. Comparative protein structure modeling by iterative alignment, model building and model assessment. Nucleic Acids Res 2003;31:3982-3992.
8. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993;234:779-815.
9. Fiser A, Sanchez R, Melo F, Sali A. Comperative protein structure modeling. In: Becker OM, MacKerell AD, Roux B, Watanabe M, editors. Computational biochemistry and biophysics. New York: Marcel Dekker; 2001. p 275-312.
10. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le TI, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Migano M. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000;289:739-745.
11. Probst WC, Snyder LA, Schuster DI, Brosius J, Sealfon SC. Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol 1992;11:1-20.
12. Du P, Salon JA, Tamm JA, Hou C, Cui W, Walker MW, Adham N, Dhanoa DS, Islam I, Vaysse PJ, Dowling B, Shifman Y, Boyle N, Rueger H, Schmidlin T, Yamaguchi Y, Branchek TA, Weinshank RL, Gluchowski C. Modeling the G-protein-coupled neuropeptide Y Y1 receptor agonist and antagonist binding sites. Protein Eng 1997;10:109-117.
13. Herzyk P, Hubbard RE. Automated method for modeling seven-helix transmembrane receptors from experimental data. Biophys J 1995;69:2419-2442.
14. Joseph MP, Maigret B, Bonnafous JC, Marie J, Scheraga HA. A computer modeling postulated mechanism for angiotensin II receptor activation. J Protein Chem 1995;14:381-398.
15. Livingstone CD, Strange PG, Naylor LH. Molecular modelling of D2-like dopamine receptors. Biochem J 1992;287:277-282.
16. Prusis P, Schioth HB, Muceniece R, Herzyk P, Afshar M, Hubbard RE, Wikberg JE. Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide. J Mol Graph Model 1997;15:307-317.
17. Baldwin JM, Schertler GF, Unger VM. An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. J Mol Biol 1997;272:144-164.
18. Unger VM, Hargrave PA, Baldwin JM, Schertler GF. Arrangement of rhodopsin transmembrane alpha-helices. Nature 1997;389:203-206.
19. Ballesteros JA, Shi L, Javitch JA. Structural mimicry in G protein-coupled receptors: implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors. Mol Pharmacol 2001;60:1-19.
20. Strahs D, Weinstein H. Comparative modeling and molecular dynamics studies of the delta, kappa and mu opioid receptors. Protein Eng 1997;10:1019-1038.
21. Green SA, Spasoff AP, Coleman RA, Johnson M, Liggett SB. Sustained activation of a G protein-coupled receptor via "anchored" agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor. J Biol Chem 1996;271:24029-24035.
22. Vaidehi N, Floriano WB, Trabanino R, Hall SE, Freddolino P, Choi EJ, Zamanakos G, Goddard WA, III. Prediction of structure and function of G protein-coupled receptors. Proc Natl Acad Sci USA 2002;99:12622-12627.
23. Filizola M, Perez JJ, Carteni-Farina M. BUNDLE: a program for building the transmembrane domains of G-protein-coupled receptors. J Comput Aided Mol Des 1998;12:111-118.
24. Archer E, Maigret B, Escrieut C, Pradayrol L, Fourmy D. Rhodopsin crystal: new template yielding realistic models of G-protein-coupled receptors? Trends Pharmacol Sci 2003;24:36-40.
25. Manivet P, Schneider B, Smith JC, Choi DS, Maroteaux L, Kellermann O, Launay JM. The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis. J Biol Chem 2002;277:17170-17178.
26. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR. NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry 2002;41:3596-3604.
27. Zhang L, DeHaven RN, Goodman M. NMR and modeling studies of a synthetic extracellular loop II of the kappa opioid receptor in a DPC micelle. Biochemistry 2002;41:61-68.
28. Underwood DJ, Strader CD, Rivero R, Patchett AA, Greenlee W, Prendergast K. Structural model of antagonist and agonist binding to the angiotensin II, AT1 subtype, G protein coupled receptor. Chem Biol 1994;1:211-221.
29. Mirzadegan T, Diehl F, Ebi B, Bhakta S, Polsky I, McCarley D, Mulkins M, Weatherhead GS, Lapierre JM, Dankwardt J, Morgans D, Jr, Wilhelm R, Jarnagin K. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem 2000;275:25562-25571.
30. Taylor WR, Jones DT, Green NM. A method for alpha-helical integral membrane protein fold prediction. Proteins 1994;18:281-294.
31. Becker OM, Shacham S, Topf M, Naor Z. A method and system for prediction of a 3D structure of a transmembrane protein. WO 02/15106.
32. Shacham S, Topf M, Avisar N, Glaser F, Marantz Y, Bar-Haim S, Noiman S, Naor Z, Becker OM. Modeling the 3D structure of GPCRs from sequence. Med Res Rev 2001;21:472-483.
33. Oshiro C, Bradley EK, Eksterowicz J, Evensen E, Lamb ML, Lanctot JK, Putta S, Stanton R, Grootenhuis PD. Performance of 3D-database molecular docking studies into homology models. J Med Chem 2004;47:764-767.
34. Shoichet BK, McGovern SL, Wei B, Irwin JJ. Lead discovery using molecular docking. Curr Opin Chem Biol 2002;6:439-446.
35. Herzyk P, Hubbard RE. A reduced representation of proteins for use in restraint satisfaction calculations. Proteins 1993;17:310-324.
36. Ponder JW, Richards FM. Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. J Mol Biol 1987;193:775-791.
37. Rost B, Casadio R, Fariselli P, Sander C. Transmembrane helices predicted at 95% accuracy. Protein Sci 1995;4:521-533.
38. Hofmann K, Stoffel W. TMbase: a database of membrane spanning proteins segments. Biol Chem 1993;374:166.
39. Rost B, Fariselli P, Casadio R. Topology prediction for helical transmembrane proteins at 86% accuracy. Protein Sci 1996;5:1704-1718.
40. Baldwin JM. The probable arrangement of the helices in G protein-coupled receptors. EMBO J 1993;12:1693-1703.
41. Attwood TK, Bradley P, Flower DR, Gaulton A, Maudling N, Mitchell AL, Moulton G, Nordle A, Paine K, Taylor P, Uddin A, Zygouri C. PRINTS and its automatic supplement, prePRINTS. Nucleic Acids Res 2003;31:400-402.
42. Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 2001;305:567-580.
43. Ballesteros JA, Weinstein H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. In: Methods in neurosciences. San Diego, CA: Academic Press; 1995. p 366-428.
44. Cohen FE, Richmond TJ, Richards FM. Protein folding: evaluation of some simple rules for the assembly of helices into tertiary structures with myoglobin as an example. J Mol Biol 1979;132:275-288.
45. Gobel U, Sander C, Schneider R, Valencia A. Correlated mutations and residue contacts in proteins. Proteins 1994;18:309-317.
46. Zhou W, Flanagan C, Ballesteros JA, Konvicka K, Davidson JS, Weinstein H, Millar RP, Sealfon SC. A reciprocal mutation supports helix 2 and helix 7 proximity in the gonadotropin-releasing hormone receptor. Mol Pharmacol 1994;45:165-170.
47. Eisenberg D, Weiss RM, Terwilliger TC. The helical hydrophobic moment: a measure of the amphiphilicity of a helix. Nature 1982;299:371-374.
48. Eisenberg D, Weiss RM, Terwilliger TC. The hydrophobic moment detects periodicity in protein hydrophobicity. Proc Natl Acad Sci USA 1984;81:140-144.
49. Cronet P, Sander C, Vriend G. Modeling of transmembrane seven helix bundles. Protein Eng 1993;6:59-64.
50. Stevens TJ, Arkin IT. Are membrane proteins "inside-out" proteins? Proteins 1999;36:135-143.
51. Burley SK, Petsko GA. Amino-aromatic interactions in proteins. FEBS Lett 1986;203:139-143.
52. Aravinda S, Shamala N, Das C, Sriranjini A, Karle IL, Balaram P. Aromatic-aromatic interactions in crystal structures of helical peptide scaffolds containing projecting phenylalanine residues. J Am Chem Soc 2003;125:5308-5315.
53. Burley SK, Petsko GA. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 1985;229:23-28.
54. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982;157:105-132.
55. Cornette JL, Cease KB, Margalit H, Spouge JL, Berzofsky JA, DeLisi C. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J Mol Biol 1987;195:659-685.
56. von Heijne G. Control of topology and mode of assembly of a polytopic membrane protein by positively charged residues. Nature 1989;341:456-458.
57. Yeagle PL. 31P nuclear magnetic resonance studies of the phospholipid-protein interface in cell membranes. Biophys J 1982;37:227-239.
58. Dunbrack RL Jr. Rotamer libraries in the 21st century. Curr Opin Struct Biol 2002;12:431-440.
59. Vendruscolo M, Najmanovich R, Domany E. Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading? Proteins 2000;38:134-148.
60. Park BH, Huang ES, Levitt M. Factors affecting the ability of energy functions to discriminate correct from incorrect folds. J Mol Biol 1997;266:831-846.
61. Park B, Levitt M. Energy functions that discriminate X-ray and near native folds from well-constructed decoys. J Mol Biol 1996;258:367-392.
62. Miyazawa S, Jernigan RL. Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. J Mol Biol 1996;256:623-644.
63. Gregoret LM, Cohen FE. Novel method for the rapid evaluation of packing in protein structures. J Mol Biol 1990;211:959-974.
64. Meurisse R, Brasseur R, Thomas A. Aromatic side-chain interactions in proteins. Near- and far-sequence His-X pairs. Biochim Biophys Acta 2003;1649:85-96.
65. Shi L, Liapakis G, Xu R, Guarnieri F, Ballesteros JA, Javitch JA. Beta2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch. J Biol Chem 2002;277:40989-40996.
66. Gromiha MM. Influence of cation-pi interactions in different folding types of membrane proteins. Biophys Chem 2003;103:251-258.
67. Zhou FX, Cocco MJ, Russ WP, Brunger AT, Engelman DM. Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nat Struct Biol 2000;7:154-160.
68. Cosson P, Lankford SP, Bonifacino JS, Klausner RD. Membrane protein association by potential intramembrane charge pairs. Nature 1991;351:414-416.
69. Segrest JP, De Loof H, Dohlman JG, Brouillette CG, Anantharamaiah GM. Amphipathic helix motif: classes and properties. Proteins 1990;8:103-117.
70. Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH, Teller E. Equations of state calculations by fast computing machine. J Chem Phys 1953;21:1087-1091.
71. Eilers M, Shekar SC, Shieh T, Smith SO, Fleming PJ. Internal packing of helical membrane proteins. Proc Natl Acad Sci U S A 2000;97:5796-5801.
72. Lin JC, Parrish W, Eilers M, Smith SO, Konopka JB. Aromatic residues at the extracellular ends of transmembrane domains 5 and 6 promote ligand activation of the G protein-coupled alpha-factor receptor. Biochemistry 2003;42:293-301.
73. Prioleau C, Visiers I, Ebersole BJ, Weinstein H, Sealfon SC. Conserved helix 7 tyrosine acts as a multistate conformational switch in the 5HT2C receptor. Identification of a novel "locked-on" phenotype and double revertant mutations. J Biol Chem 2002;277:36577-36584.
74. Chothia C. Principles that determine the structure of proteins. Annu Rev Biochem 1984;53:537-572.
75. Bowie JU. Helix packing in membrane proteins. J Mol Biol 1997;272:780-789.
76. Spencer RH, Rees DC. The alpha-helix and the organization and gating of channels. Annu Rev Biophys Biomol Struct 2002;31:207-233.
77. Insight II, Version 2000.1. San Diego: Accelrys Inc.
78. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 1983;4:187-217.
79. Hwang MJ, Stockfisch TP, Hagler AT. Derivation and characterization of a class II force field, CFF93, for the alkyl functional group and alkane molecules. J Am Chem Soc 1994;116:2515-2525.
80. Maple JR, Hwang MJ, Jalkanen KJ, Stockfisch TP. Derivation of class II force fields. V. Quantum force field for amides, peptides, and related compounds. J Comp Chem 2003;19:458.
81. Visiers I, Ballesteros JA, Weinstein H. Three-dimensional representations of G protein-coupled receptor structures and mechanisms. Methods Enzymol 2002;343:329-371.
82. Visiers I, Braunheim BB, Weinstein H. Prokink: a protocol for numerical evaluation of helix distortions by proline. Protein Eng 2000;13:603-606.
83. Bachar M, Becker OM. Protein-induced membrane disorder: a molecular dynamics study of melittin in a dipalmitoylphosphatidylcholine bilayer. Biophys J 2000;78:1359-1375.
84. Bachar M, Becker OM. Melittin at a membrane/water interface: effects on water orientation and water penetration. J Chem Phys 1999;111:8672-8685.
85. CONCORD, Version 4.04 Tripos Inc. St. Louis, MO 63144.
86. SYBYL, Version 6.8. Tripos Inc. St. Louis, MO 63144.
87. ACD v.2001-1, MDL Information Systems Inc. San Leandro, CA 94577.
88. LeadQuest, Tripos Inc. St. Louis, MO 63144
89. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3-25.
90. DOCK, Version 4.0. San Francisco: Molecular Design Institute, University of California.
91. CONFORT, Version 4.1 Tripos Inc. St. Louis, MO 63144.
92. Shi L, Javitch JA. The binding site of aminergic G protein-coupled receptors: the transmembrane segments and second extracellular loop. Annu Rev Pharmacol Toxicol 2002;42:437-467.
93. Piela L, Nemethy G, Scheraga HA. Proline-induced constraints in alpha-helices. Biopolymers 1987;26:1587-1600.
94. Kumar S, Bansal M. Geometrical and sequence characteristics of alpha-helices in globular proteins. Biophys J 1998;75:1935-1944.
95. Gray TM, Matthews BW. Intrahelical hydrogen bonding of serine, threonine and cysteine residues within alpha-helices and its relevance to membrane-bound proteins. J Mol Biol 1984;175:75-81.
96. Xu W, Ozdener F, Li JG, Chen C, de Riel JK, Weinstein H, Liu-Chen LY. Functional role of the spatial proximity of Asp114(2.50) in TMH 2 and Asn332(7.49) in TMH 7 of the mu opioid receptor. FEBS Lett 1999;447:318-324.
97. Flanagan CA, Zhou W, Chi L, Yuen T, Rodic V, Robertson D, Johnson M, Holland P, Millar RP, Weinstein H, Mitchell R, Sealfon SC. The functional microdomain in transmembrane helices 2 and 7 regulates expression, activation, and coupling pathways of the gonadotropin-releasing hormone receptor. J Biol Chem 1999;274:28880-28886.
98. Sealfon SC, Chi L, Ebersole BJ, Rodic V, Zhang D, Ballesteros JA, Weinstein H. Related contribution of specific helix 2 and 7 residues to conformational activation of the serotonin 5-HT2A receptor. J Biol Chem 1995;270:16683-16688.
99. Javitch JA, Fu D, Chen J. Residues in the fifth membrane-spanning segment of the dopamine D2 receptor exposed in the binding-site crevice. Biochemistry 1995;34:16433-16439.
100. Cox BA, Henningsen RA, Spanoyannis A, Neve RL, Neve KA. Contributions of conserved serine residues to the interactions of ligands with dopamine D2 receptors. J Neurochem 1992;59:627-635.
101. Shi L, Simpson MM, Ballesteros JA, Javitch JA. The first transmembrane segment of the dopamine D2 receptor: accessibility in the binding-site crevice and position in the transmembrane bundle. Biochemistry 2001;40:12339-12348.
102. Javitch JA, Ballesteros JA, Weinstein H, Chen J. A cluster of aromatic residues in the sixth membrane-spanning segment of the dopamine D2 receptor is accessible in the binding-site crevice. Biochemistry 1998;37:998-1006.
103. Bryant SH, Altschul SF. Statistics of sequence-structure threading. Curr Opin Struct Biol 1995;5:236-244.
104. Bowie JU, Luthy R, Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science 1991;253:164-170.
105. Becker OM. Principal coordinate maps of molecular potential energy surfaces. J Comput Chem 1998;19:1255-1267.
106. Javitch JA, Li X, Kaback J, Karlin A. A cysteine residue in the third membrane-spanning segment of the human D2 dopamine receptor is exposed in the binding-site crevice. Proc Natl Acad Sci USA 1994;91:10355-10359.
107. Simpson MM, Ballesteros JA, Chiappa V, Chen J, Suehiro M, Hartman DS, Godel T, Snyder LA, Sakmar TP, Javitch JA. Dopamine D4/D2 receptor selectivity is determined by A divergent aromatic microdomain contained within the second, third, and seventh membrane-spanning segments. Mol Pharmacol 1999;56:1116-1126.
108. Strader CD, Sigal IS, Candelore MR, Rands E, Hill WS, Dixon RA. Conserved aspartic acid residues 79 and 113 of the beta-adrenergic receptor have different roles in receptor function. J Biol Chem 1988;263:10267-10271.
109. Trumpp-Kallmeyer S, Hoflack J, Bruinvels A, Hibert M. Modeling of G-protein-coupled receptors: application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors. J Med Chem 1992;35:3448-3462.
110. Mansour A, Meng F, Meador-Woodruff JH, Taylor LP, Civelli O, Akil H. Site-directed mutagenesis of the human dopamine D2 receptor. Eur J Pharmacol 1992;227:205-214.
111. Ballesteros JA, Deupi X, Olivella M, Haaksma EE, Pardo L. Serine and threonine residues bend alpha-helices in the chi(1) = g(-) conformation. Biophys J 2000;79:2754-2760.
112. Savarese TM, Wang CD, Fraser CM. Site-directed mutagenesis of the rat m1 muscarinic acetylcholine receptor. Role of conserved cysteines in receptor function. J Biol Chem 1992;267:11439-11448.
113. Guo W, Shi L, Javitch JA. The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem 2003;278:4385-4388.
114. Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, Engel A. Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 2003;278:21655-21662.
115. Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 1996;274:768-770.
116. Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK. Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Natl Acad Sci USA 2001;98:5997-6002.
117. Huang P, Li J, Chen C, Visiers I, Weinstein H, Liu-Chen LY. Functional role of a conserved motif in TM6 of the rat mu opioid receptor: constitutively active and inactive receptors result from substitutions of Thr6.34(279) with Lys and Asp. Biochemistry 2001;40:13501-13509.
118. Huang P, Visiers I, Weinstein H, Liu-Chen LY. The local environment at the cytoplasmic end of TM6 of the mu opioid receptor differs from those of rhodopsin and monoamine receptors: introduction of an ionic lock between the cytoplasmic ends of helices 3 and 6 by a L6.30(275)E mutation inactivates the mu opioid receptor and reduces the constitutive activity of its T6.34(279)K mutant. Biochemistry 2002;41:11972-11980.
119. Zhou W, Rodic V, Kitanovic S, Flanagan CA, Chi L, Weinstein H, Maayani S, Millar RP, Sealfon SC. A locus of the gonadotropin-releasing hormone receptor that differentiates agonist and antagonist binding sites. J Biol Chem 1995;270:18853-18857.
120. Lu ZL, Saldanha JW, Hulme EC. Transmembrane domains 4 and 7 of the M(1) muscarinic acetylcholine receptor are critical for ligand binding and the receptor activation switch. J Biol Chem 2001;276:34098-34104.
121. Elling CE, Thirstrup K, Holst B, Schwartz TW. Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor. Proc Natl Acad Sci U S A 1999;96:12322-12327.
122. Teller DC, Okada T, Behnke CA, Palczewski K, Stenkamp RE. Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry 2001;40:7761-7772.
123. Cerda-Reverter JM, Martinez-Rodriguez G, Zanuy S, Carrillo M, Larhammar D. Molecular evolution of the neuropeptide Y (NPY) family of peptides: cloning of three NPY-related peptides from the sea bass (Dicentrarchus labrax). Regul Pept 2000;95:25-34.
124. Larhammar D. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul Pept 1996;65:165-174.
125. Parker SL, Crowley WR. Central stimulation of oxytocin release in the lactating rat: interaction of neuropeptide Y with alpha-1-adrenergic mechanisms. Endocrinology 1993;132:658-666.
126. Kalra SP, Fuentes M, Fournier A, Parker SL, Crowley WR. Involvement of the Y-1 receptor subtype in the regulation of luteinizing hormone secretion by neuropeptide Y in rats. Endocrinology 1992;130:3323-3330.
127. Kannoa T, Kanatani A, Keen SL, Arai-Otsuki S, Haga Y, Iwama T, Ishihara A, Sakuraba A, Iwaasa H, Hirose M, Morishima H, Fukami T, Ihara M. Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J-104870 on human Y1 receptors. Peptides 2001;22:405-413.
128. Sautel M, Rudolf K, Wittneben H, Herzog H, Martinez R, Munoz M, Eberlein W, Engel W, Walker P, Beck-Sickinger AG. Neuropeptide Y and the nonpeptide antagonist BIBP 3226 share an overlapping binding site at the human Y1 receptor. Mol Pharmacol 1996;50:285-292.
129. Schertler GF, Villa C, Henderson R. Projection structure of rhodopsin. Nature 1993;362:770-772.
130. Sautel M, Martinez R, Munoz M, Peitsch MC, Beck-Sickinger AG, Walker P. Role of a hydrophobic pocket of the human Y1 neuropeptide Y receptor in ligand binding. Mol Cell Endocrinol 1995;112:215-222.
131. Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V. The tachykinin peptide family. Pharmacol Rev 2002;54:285-322.
132. Fong TM, Huang RR, Yu H, Strader CD. Mapping the ligand binding site of the NK-1 receptor. Regul Pept 1993;46:43-48.
133. Cascieri MA, Shiao LL, Mills SG, MacCoss M, Swain CJ, Yu H, Ber E, Sadowski S, Wu MT, Strader CD, et al. Characterization of the interaction of diacylpiperazine antagonists with the human neurokinin-1 receptor: identification of a common binding site for structurally dissimilar antagonists. Mol Pharmacol 1995;47:660-665.
134. Holst B, Zoffmann S, Elling CE, Hjorth SA, Schwartz TW. Steric hindrance mutagenesis versus alanine scan in mapping of ligand binding sites in the tachykinin NK1 receptor. Mol Pharmacol 1998;53:166-175.
135. Fong TM, Yu H, Cascieri MA, Underwood D, Swain CJ, Strader CD. The role of histidine 265 in antagonist binding to the neurokinin-1 receptor. J Biol Chem 1994;269:2728-2732.
136. Gether U, Johansen TE, Snider RM, Lowe JA, III, Nakanishi S, Schwartz TW. Different binding epitopes on the NK1 receptor for substance P and non-peptide antagonist. Nature 1993;362:345-348.
137. Gether U, Emonds-Alt X, Breliere JC, Fujii T, Hagiwara D, Pradier L, Garret C, Johansen TE, Schwartz TW. Evidence for a common molecular mode of action for chemically distinct nonpeptide antagonists at the neurokinin-1 (substance P) receptor. Mol Pharmacol 1994;45:500-508.
138. Snider RM, Constantine JW, Lowe JA, III, Longo KP, Lebel WS, Woody HA, Drozda SE, Desai MC, Vinick FJ, Spencer RW, et al. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 1991;251:435-437.
139. Fong TM, Yu H, Strader CD. Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. J Biol Chem 1992;267:25668-25671.
140. Fong TM, Huang RR, Strader CD. Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. J Biol Chem 1992;267:25664-25667.
141. Fong TM, Yu H, Huang RR, Strader CD. The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides. Biochemistry 1992;31:11806-11811.
142. Elling CE, Nielsen SM, Schwartz TW. Conversion of antagonist-binding site to metal-ion site in the tachykinin NK-1 receptor. Nature 1995;374:74-77.
143. Yang AS, Honig B. An integrated approach to the analysis and modeling of protein sequences and structures. I. Protein structural alignment and a quantitative measure for protein structural distance. J Mol Biol 2000;301:665-678.
144. Wilson CA, Kreychman J, Gerstein M. Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores. J Mol Biol 2000;297:233-249.
145. Yang AS, Honig B. An integrated approach to the analysis and modeling of protein sequences and structures. II. On the relationship between sequence and structural similarity for proteins that are not obviously related in sequence. J Mol Biol 2000;301:679-689.
146. Lu ZL, Saldanha JW, Hulme EC. Seven-transmembrane receptors: crystals clarify. Trends Pharmacol Sci 2002;23:140-146.
147. Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ, Jr. Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor. Mol Pharmacol 2002;62:38-47.
148. Ye J, Kohli LL, Stone MJ. Characterization of binding between the chemokine eotaxin and peptides derived from the chemokine receptor CCR3. J Biol Chem 2000;275:27250-27257.
149. SWISS-MODEL 7TM. 2003. Retrieved Internet Communication. http://www.expasy.org/swissmod/SM_GPCRInformation.html
150. Paterlini MG. Structure modeling of the chemokine receptor CCR5: implications for ligand binding and selectivity. Biophys J 2002;83:3012-3031.
151. Berkhout TA, Blaney FE, Bridges AM, Cooper DG, Forbes IT, Gribble AD, Groot PH, Hardy A, Ife RJ, Kaur R, Moores KE, Shillito H, Willetts J, Witherington J. CCR2: Characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem 2003;46:4070-4086.
152. George SR, O'Dowd BF, Lee SP. G-protein-coupled receptor oligomerization and its potential for drug discovery. Nat Rev Drug Discov 2002;1:808-820.
153. Pizard A, Marchetti J, Allegrini J, Alhenc-Gelas F, Rajerison RM. Negative cooperativity in the human bradykinin B2 receptor. J Biol Chem 1998;273:1309-1315.
154. Freedman SB, Patel S, Marwood R, Emms F, Seabrook GR, Knowles MR, McAllister G. Expression and pharmacological characterization of the human D3 dopamine receptor. J Pharmacol Exp Ther 1994;268:417-426.
155. Sautel F, Griffon N, Levesque D, Pilon C, Schwartz JC, Sokoloff P. A functional test identifies dopamine agonists selective for D3 versus D2 receptors. Neuroreport 1995;6:329-332.
156. Sokoloff P, Giros B, Martres MP, Andrieux M, Besancon R, Pilon C, Bouthenet ML, Souil E, Schwartz JC. Localization and function of the D3 dopamine receptor. Arzneimittelforschung 1992;42:224-230.
157. Seeman P, Corbett R, Van Tol HH. Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. Neuropsychopharmacology 1997;16:93-110.
158. Lejeune F, Newman-Tancredi A, Audinot V, Millan MJ. Interactions of (+)- and (-)-8- and 7-hydroxy-2-(di-n-propylamino)tetralin at human (h)D3, hD2 and h serotoninlA receptors and their modulation of the activity of serotoninergic and dopaminergic neurones in rats. J Pharmacol Exp Ther 1997;280:1241-1249.
159. Richelson E, Nelson A. Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol 1984;103:197-204.
160. Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 1994;114:559-565.
161. Seeman P, Van Tol HH. Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand. Eur J Pharmacol 1995;291:59-66.
162. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-423.
163. Vallone D, Picetti R, Borrelli E. Structure and function of dopamine receptors. Neurosci Biobehav Rev 2000;24:125-132.
164. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. Differential actions in antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther 2002;303:791-804.
165. Wieland HA, Engel W, Eberlein W, Rudolf K, Doods HN. Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents. Br J Pharmacol 1998;125:549-555.
166. Zarrinmayeh H, Zimmerman DM, Cantrell BE, Schober DA, Bruns RF, Gackenheimer SL, Ornstein PL, Hipskind PA, Britton TC, Gehlert DR. Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists. Bioorg Med Chem Lett 1999;9:647-652.
167. Zarrinmayeh H, Nunes AM, Ornstein PL, Zimmerman DM, Arnold MB, Schober DA, Gackenheimer SL, Bruns RF, Hipskind PA, Britton TC, Cantrell BE, Gehlert DR. Synthesis and evaluation of a series of novel 2-[(4-chlorophenoxy)methyl] benzimidazoles as selective neuropeptide Y Y1 receptor antagonists. J Med Chem 1998;41:2709-2719.
168. Hipskind PA, Lobb KL, Nixon JA, Britton TC, Bruns RF, Catlow J, Dieckman-McGinty DK, Gackenheimer SL, Gitter BD, Iyengar S, Schober DA, Simmons RM, Swanson S, Zarrinmayeh H, Zimmerman DM, Gehlert DR. Potent and selective 1,2,3-trisubstituted indole NPY Y-1 antagonists. J Med Chem 1997;40:3712-3714.
169. Zhang W, Lundberg JM, Thoren P. Neuropeptide Y Y1 receptor antagonist (BIBP 3226) attenuates stress evoked tachycardia in conscious spontaneously hypertensive rats. Cardiovasc Drugs Ther 1997;11:801-806.
170. Kannoa T, Kanatani A, Keen SL, Arai-Otsuki S, Haga Y, Iwama T, Ishihara A, Sakuraba A, Iwaasa H, Hirose M, Morishima H, Fukami T, Ihara M. Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J-104870 on human Y1 receptors. Peptides 2001;22:405-413.
171. Kanatani A, Hata M, Mashiko S, Ishihara A, Okamoto O, Haga Y, Ohe T, Kanno T, Murai N, Ishii Y, Fukuroda T, Fukami T, Ihara M. A typical Y1 receptor regulates feeding behaviors: effects of a potent and selective Y1 antagonist, J-115814. Mol Pharmacol 2001;59:501-505.
172. Lecklin A, Lundell I, Paananen L, Wikberg JE, Mannisto PT, Larhammar D. Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea-pig. Br J Pharmacol 2002;135:2029-2037.
173. Hong Y, Gregor V, Ling AL, Tompkins EV, Porter J, Chou TS, Paderes G, Peng Z, Hagaman C, Anderes K, Luthin D, May J. Synthesis and biological evaluation of novel guanylurea compounds as potent NPY Y1 receptor antagonist. 217th ACS National Meeting (Anaheim, Spring 1999). Abstract MEDI-108.
174. Tattersall FD, Rycroft W, Francis B, Pearce D, Merchant K, MacLeod AM, Ladduwahetty T, Keown L, Swain C, Baker R, Cascieri M, Ber E, Metzger J, MacIntyre DE, Hill RG, Hargreaves RJ. Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacology 1996;35:1121-1129.
175. Beattie DT, Beresford IJ, Connor HE, Marshall FH, Hawcock AB, Hagan RM, Bowers J, Birch PJ, Ward P. The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist. Br J Pharmacol 1995;116:3149-3157.
176. Dinnell K, Chicchi GG, Dhar MJ, Elliott JM, Hollingworth GJ, Kurtz MM, Ridgill MP, Rycroft W, Tsao KL, Williams AR, Swain CJ. 2-Aryl indole NK1 receptor antagonists: optimisation of the 2-aryl ring and the indole nitrogen substituent. Bioorg Med Chem Lett 2001;11:1237-1240.
177. Walpole C, Ko SY, Brown M, Beattie D, Campbell E, Dickenson F, Ewan S, Hughes GA, Lemaire M, Lerpiniere J, Patel S, Urban L. 2-Nitrophenylcarbamoyl-(S) -prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N - methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models. J Med Chem 1998;41:3159-3173.
178. Boyle S, Guard S, Higginbottom M, Horwell DC, Howson W, McKnight AT, Martin K, Pritchard MC, O'Toole J, Raphy J, et al. Rational design of high affinity tachykinin NK1 receptor antagonists. Bioorg Med Chem 1994;2:357-370.
179. Emonds-Alt X, Doutremepuich JD, Heaulme M, Neliat G, Santucci V, Steinberg R, Vilain P, Bichon D, Ducoux JP, Proietto V, et al. In vitro and in vivo biological activities of SR140333, a novel potent non-peptide tachykinin NK1 receptor antagonist. Eur J Pharmacol 1993;250:403-413.
180. Harrison T, Owens AP, Williams BJ, Swain CJ, Williams A, Carlson EJ, Rycroft W, Tattersall FD, Cascieri MA, Chicchi GG, Sadowski S, Rupniak NM, Hargreaves RJ. An orally active, water-soluble neurokinin-1 receptor antagonist suitable for both intravenous and oral clinical administration. J Med Chem 2001;44:4296-4299.
181. Stevenson GI, Huscroft I, MacLeod AM, Swain CJ, Cascieri MA, Chicchi GG, Graham MI, Harrison T, Kelleher FJ, Kurtz M, Ladduwahetty T, Merchant KJ, Metzger JM, MacIntyre DE, Sadowski S, Sohal B, Owens AP. 4,4-Disubstituted piperidine high-affinity NK1 antagonists: structure-activity relationships and in vivo activity. J Med Chem 1998;41:4623-4635.
182. Natsugari H, Ikeura Y, Kamo I, Ishimaru T, Ishichi Y, Fujishima A, Tanaka T, Kasahara F, Kawada M, Doi T. Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK(1) receptor antagonists: synthesis, antagonistic activity, and effects on bladder functions. J Med Chem 1999;42:3982-3993.
183. Ashwood VA, Field MJ, Horwell DC, Julien-Larose C, Lewthwaite RA, McCleary S, Pritchard MC, Raphy J, Singh L. Utilization of an intramolecular hydrogen bond to increase the CNS penetration of an NK(1) receptor antagonist. J Med Chem 2001;44:2276-2285.
184. Ikeura Y, Ishichi Y, Tanaka T, Fujishima A, Murabayashi M, Kawada M, Ishimaru T, Kamo I, Doi T, Natsugari H. Axially chiral N-benzyl-N,7-dimethyl-5- phenyl-1, 7-naphthyridine-6-carboxamide derivatives as tachykinin NK1 receptor antagonists: determination of the absolute stereochemical requirements. J Med Chem 1998;41:4232-4239.
185. Papp M, Vassout A, Gentsch C. The NK1-receptor antagonist NKP608 has an antidepressant-like effect in the chronic mild stress model of depression in rats. Behav Brain Res 2000;115:19-23.
186. Kudlacz EM, Shatzer SA, Knippenberg RW, Logan DE, Poirot M, van Giersbergen PL, Burkholder TP. In vitro and in vivo characterization of MDL 105,212A, a nonpeptide NK-1/NK-2 tachykinin receptor antagonist. J Pharmacol Exp Ther 1996;277:840-851.
187. 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;21:4377-4392.