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Review

The role of experimental and computational structural approaches in 7TM drug discovery

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Bibliography

  • Overington J, Al-Lazikani B, Hopkins A. How many drug targets are there? Nat Rev Drug Discov 2006;5:993-6
  • Salon JA, Lodowski DT, Palczewski K. The significance of G protein-coupled receptor crystallography for drug discovery. Pharmacol Rev 2011;63:901-37
  • Conn PJ. Physiological roles and therapeutic potential of metabotropic glutamate receptors. Ann NY Acad Sci 2003;1003:12-21
  • Premont RT, Gainetdinov RR, Physiological Roles of G. Protein–coupled receptor kinases and arrestins. Ann Rev Physiol 2007;69:511-34
  • Siehler S, Milligan G. editors. G Protein-coupled receptors: structure, signaling, and physiology. Cambridge University Press, New York, NY; 2010
  • Granier S, Kobilka B. A new era of GPCR structural and chemical biology. Nat Chem Biol 2012;8(8):670-3
  • Muller DJ, Wu N, Palczewski K. Vertebrate membrane proteins: structure, function, and insights from biophysical approaches. Pharmacol Rev 2008;60:43-78
  • Montaner S, Kufareva I, Abagyan R, et al. Molecular mechanisms deployed by virally encoded G protein-coupled receptors in human diseases. Annu Rev Pharmacol Toxicol 2013;53:331-54
  • Dorsum RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer 2007;7:79-94
  • Schöneberg T, Schulz A, Biebermann H, et al. Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol Ther 2004;104:173-206
  • Seifert R, Wenzel-Seifert K. Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn Schmiedebergs Arch Pharmacol 2002;366:381-416
  • Bjarnadóttir TK, Gloriam DE, Hellstrand SH, et al. Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics 2006;88(3):263-73
  • Topiol S. X-ray structural information of GPCRs in drug design: what are the limitations and where do we go? Expert Opin Drug Discov 2013;8(6):607-20
  • Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000;289:739-45
  • Rasmussen SGF, Choi H-J, Rosenbaum DM, et al. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 2007;450:383-8
  • Cherezov V, Rosenbaum DM, Hanson MA, et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 2007;318:1258-65
  • Lagerström MC, Schiöth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 2008;7(4):339-57. Erratum in Nat Rev Drug Discov 2008;7(6):542
  • Lundstrom K. An overview on GPCRs and drug discovery: structure-based drug design and structural biology on GPCRs. In: Leifert WR, editor, G Protein-Coupled Receptors in Drug Discovery. Humana Press, New York, NY; 2009. p. 51-66
  • Jacobson K, Costanzi S. New insights for drug design from the X-ray crystallographic structures of G-protein-coupled receptors. Mol Pharmacol 2012;82:361-71
  • Shoichet BK, Kobilka BK. Structure-based drug screening for G-protein-coupled receptors. Trends Pharmacol Sci 2012;33(5):268-72
  • Audet M, Bouvier M. Restructuring G-protein coupled receptor activation. Cell 2012;151:14-23
  • Andrews SP, Brown GA, Christopher JA. Structure-based and fragment-based gpcr drug discovery. ChemMedChem 2014;9:256-75
  • Tautermann CS. GPCR structures in drug design, emerging opportunities with new structures. Bioorg Med Chem Lett 2014;24(17):4073-9
  • Rosenbaum DM, Cherezov V, Hanson MA, et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 2007;318(5854):1266-73
  • Zou Y, Weis WI, Kobilka BK. N-Terminal T4 lysozyme fusion facilitates crystallization of a G protein coupled receptor. PLoS One 2012;7(10):e46039
  • Mathew E, Ding FX, Naider F, et al. Functional fusions of T4 lysozyme in the third intracellular loop of a G protein-coupled receptor identified by a random screening approach in yeast. Protein Eng Des Sel 2013;26(1):59-71
  • Rasmussen SGF, DeVree BT, Zou Y, et al. Crystal structure of the beta2 adrenergic receptor–Gs protein complex. Nature 2011;477:549-55
  • Choe H-W, Kim YJ, Park JH, et al. Crystal structure of metarhodopsin II. Nature 2011;471:651-5
  • Standfuss J, Edwards PC, D’Antona A, et al. The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 2011;471:656-60
  • Singhal A, Ostermaier MK, Vishnivetskiy SA, et al. Insights into congenital stationary night blindness based on the structure of G90D rhodopsin. EMBO Rep 2013;14(6):520-6
  • Rasmussen SG, Choi HJ, Fung JJ, et al. Structure of a nanobody-stabilized active state of the beta2 adrenoceptor. Nature 2011;469(7329):175-80
  • Rosenbaum DM, Zhang C, Lyons J, et al. Structure and function of an irreversible agonist-beta2 adrenoceptor complex. Nature 2011;469(7329):236-40
  • Park SH, Das BB, Casagrande F, et al. Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature 2012;491:779-83
  • Doré AS, Robertson N, Errey JC, et al. Structure of the adenosine A2A receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure 2011;19(9):1283-93
  • Kahsai AW, Xiao K, Rajagopal S, et al. Multiple ligand-specific conformations of the beta2-adrenergic receptor. Nat Chem Biol 2011;7(10):692-700
  • Perez-Aguilar JM, Shan J, LeVine MV, et al. A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2. J Am Chem Soc 2014;136:16044-54
  • Prasanna X, Chattopadhyay A, Sengupta D. Cholesterol modulates the dimer interface of the beta2-adrenergic receptor via cholesterol occupancy sites. Biophys J 2014;106(6):1290-300
  • González-Maeso J, Ang RL, Yuen T, et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008;452(7183):93-7
  • Liu Z, Crider AM, Ansbro D, et al. A structure-based approach to understanding somatostatin receptor-4 agonism (sst4). J Chem Inf Model 2012;52(1):171-86
  • Hollenstein K, Kean J, Bortolato A, et al. Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature 2013;499:438-43
  • Siu FY, He M, de Graaf C, et al. Structure of the human glucagon class B G-protein-coupled receptor. Nature 2013;499(7459):444-9
  • Hollenstein K, de Graaf C, Bortolato A, et al. Insights into the structure of class B GPCRs. Trends Pharmacol Sci 2014;35(1):12-22
  • Ballesteros JA, Jensen AD, Liapakis G, et al. Activation of the beta2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 2001;276:29171-7
  • Ballesteros JA, Weinstein H. [19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Meth Neurosci 1995;25:366-428
  • Scheerer P, Park JH, Hildebrand PW, et al. Crystal structure of opsin in its G-protein-interacting conformation. Nature 2008;455:497-502
  • Chien EYT, Liu W, Zhao Q, et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 2010;330:1091-5
  • Wu H, Wang C, Gregory KJ, et al. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science 2014;344(6179):58-64
  • Doré AS, Okrasa K, Patel JC, et al. Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature 2014;511(7511):557-62
  • Wang C, Wu H, Katritch V, et al. Structure of the human smoothened receptor bound to an antitumour agent. Nature 2013;497:338-43
  • Wang C, Wu H, Evron T, et al. Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. Nat Commun 2014;5:4355
  • Jaakola V-P, Griffith MT, Hanson MA, et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 2008;322(5905):1211-17
  • Hino T, Arakawa T, Iwanari H, et al. G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody. Nature 2012;482(7384):237-40
  • Liu W, Chun E, Thompson AA, et al. Structural basis for allosteric regulation of GPCRs by sodium ions. Science 2012;337(6091):232-6
  • Rodríguez D, Piñeiro Á, Gutiérrez-de-Terán H. Molecular dynamics simulations reveal insights into key structural elements of adenosine receptors. Biochemistry 2011;50:4194-208
  • Huber T, Menon S, Sakmar TP. Structural basis for ligand binding and specificity in adrenergic receptors: Implications for GPCR-targeted drug discovery. Biochemistry 2008;47:11013-23
  • Vanni S, Neri M, Tavernelli I, et al. Observation of “ionic lock” formation in molecular dynamics simulations of wild-type beta1 and beta2 adrenergic receptors. Biochemistry 2009;48:4789-97
  • Dror RO, Arlow DH, Borhani DW, et al. Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations. Proc Natl Acad Sci USA 2009;106:4689-94
  • Romo TD, Grossfield A, Pitman MC. Concerted interconversion between ionic lock substates of the beta2 adrenergic receptor revealed by microsecond timescale molecular dynamics. Biophys J 2010;98:76-84
  • Valentin-Hansen L, Groenen M, Nygaard R, et al. The arginine of the DRY motif in transmembrane segment III functions as a balancing micro-switch in the activation of the beta2-adrenergic receptor. J Biol Chem 2012;287(38):31973-82
  • Howard MJ, Hughes RJ, Motulsky HJ, et al. Interactions of amiloride with alpha- and beta-adrenergic receptors: amiloride reveals an allosteric site on alpha 2-adrenergic receptors. Mol Pharmacol 1987;32:53-8
  • Gutiérrez-de-Terán H, Massink A, Rodríguez D, et al. The role of a sodium ion binding site in the allosteric modulation of the A(2A) adenosine G protein-coupled receptor. Structure 2013;21(12):2175-85
  • Lenselink EB, Beuming T, Sherman W, et al. Selecting an optimal number of binding site waters to improve virtual screening enrichments against the adenosine A2A receptor. J Chem Inf Model 2014;54(6):1737-46
  • de Lera Ruiz M, Lim YH, Zheng J. Adenosine A2A receptor as a drug discovery target. J Med Chem 2014;57(9):3623-50
  • Sabbadin D, Ciancetta A, Moro S. Perturbation of fluid dynamics properties of water molecules during G protein-coupled receptor–ligand recognition: the human A2A adenosine receptor as a key study. J Chem Inf Model 2014;54(10):2846-55
  • Massink A, Gutiérrez-de-Terán H, Lenselink EB, et al. Sodium ion binding pocket mutations and adenosine A2A receptor function. Mol Pharmacol 2015;87(2):305-13
  • Schwartz TW, Frimurer TM, Holst B, et al. Molecular mechanism of 7TM receptor activation – a global toggle switch model. Annu Rev Pharmacol Toxicol 2006;46:481-519
  • Shimamura T, Shiroishi M, Weyand S, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature 2011;475(7354):65-70
  • Haga K, Kruse AC, Asada H, et al. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 2012;482(7386):547-51
  • Xu F, Wu H, Katritch V, et al. Structure of an agonist-bound human A2A adenosine receptor. Science 2011;332(6027):322-7
  • Goudet C, Gaven F, Kniazeff J, et al. Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors. Proc Natl Acad Sci USA 2004;101(1):378-83
  • Binet V, Brajon C, Le Corre L, et al. The heptahelical domain of GABAB2 is activated directly by CGP7930, a positive allosteric modulator of the GABAB receptor. J Biol Chem 2004;279(28):29085-91
  • Kruse AC, Hu J, Pan AC, et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 2012;482(7386):552-6
  • Warne T, Moukhametzianov R, Baker JG, et al. The structural basis for agonist and partial agonist action on a beta1-adrenergic receptor. Nature 2011;469(7329):241-4
  • Lebon G, Warne T, Edwards PC, et al. Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 2011;474(7352):521-5
  • Wacker D, Wang C, Katritch V, et al. Structural features for functional selectivity at serotonin receptors. Science 2013;340(6132):615-19
  • Martí-Solano M, Iglesias A, de Fabritiis G, et al. Detection of new biased agonists for the serotonin 5-HT2A receptor: modeling and experimental validation. Mol Pharmacol 2015;87(4):740-6
  • Hanson MA, Roth CB, Jo E, et al. Crystal structure of a lipid G protein-coupled receptor. Science 2012;335(6070):851-5
  • Zhang C, Srinivasan Y, Arlow DH, et al. High-resolution crystal structure of human protease-activated receptor 1. Nature 2012;492(7429):387-92
  • Srivastava A, Yano JK, Hirozane Y, et al. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature 2014;513:124-7
  • Zhang D, Gao Z, Jacobson K, et al. Two disparate ligand-binding sites in the human P2Y1 receptor. Nature 2015;520:317-21
  • Topiol S, Sabio M. Use of the x-ray structure of the Beta2-adrenergic receptor for drug discovery. Bioorg Med Chem Lett 2008;18:1598-602
  • 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;18:5391-5
  • Kolb P, Rosenbaum DM, Irwin JJ, et al. Structure-based discovery of beta2-adrenergic receptor ligands. Proc Natl Acad Sci USA 2009;106:6843-8
  • Carlsson J, Yoo L, Gao Z-G, et al. Structure-based discovery of A2a adenosine receptor ligands. J Med Chem 2010;3748-55
  • Irwin JJ, Shoichet BK. ZINC – a free database of commercially available compounds for virtual screening. J Chem Inf Model 2005;45:177-82
  • Katritch V, Jaakola V-P, Lane JR, et al. Structure-based discovery of novel chemotypes for adenosine A2a receptor antagonists. J Med Chem 2010;53:1799-809
  • Sanders MP, Roumen L, van der Horst E, et al. A prospective cross-screening study on G-protein-coupled receptors: lessons learned in virtual compound library design. J Med Chem 2012;55(11):5311-25
  • Carlsson J, Coleman RG, Setola V, et al. Ligand Discovery from a dopamine D3 receptor homology model and crystal structure. Nat Chem Biol 2011;7:769-78
  • Mysinger MM, Weiss DR, Ziarek JJ, et al. Structure-based ligand discovery for the protein–protein interface of chemokine receptor CXCR4. Proc Natl Acad Sci USA 2012;109:5517-22
  • de Graaf C, Kooistra AJ, Vischer HF, et al. Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor. J Med Chem 2011;54(23):8195-206
  • Michino M, Abola E, Brooks CL3rd, et al. Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008. Nat Rev Drug Discov 2009;8(6):455-63
  • Kufareva I, Rueda M, Katritch V, et al. Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment. Structure 2011;19:1108-26
  • Nguyen ED, Norn C, Frimurer TM, et al. Assessment and challenges of ligand docking into comparative models of G-protein coupled receptors. PLOS One 2013;8(7):e67302
  • Katritch V, Kufareva I, Abagyan R. Structure based prediction of subtype-selectivity for adenosine receptor antagonists. Neuropharmacology 2011;60(1):108-15
  • Marco I, Valhondo M, Martín-Fontecha M, et al. New serotonin 5-HT1A receptor agonists with neuroprotective effect against ischemic cell damage. J Med Chem 2011;54(23):7986-99
  • Tosh DK, Paoletta S, Deflorian F, et al. Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity. J Med Chem 2012;55(18):8075-90
  • Hou X, Majik M, Kim K, et al. Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A2a and A3 adenosine receptor ligands. J Med Chem 2012;55(1):342-56
  • 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(16):4978-85
  • Katritch V, Reynolds KA, Cherezov V, et al. 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(4):307-18
  • Newman AH, Beuming T, Banala AK, et al. Molecular determinants of selectivity and efficacy at the dopamine D3 receptor. J Med Chem 2012;55(15):6689-99
  • Jo E, Bhatarai B, Repetto E, et al. Novel selective allosteric and bitopic ligands for the S1P3 receptor. ACS Chem Biol 2012;7(12):1975-83
  • Bonifazi A, Yano H, Del Bello F, et al. Synthesis and biological evaluation of a novel series of heterobivalent muscarinic ligands based on xanomeline and 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1). J Med Chem 2014;57(21):9065-77
  • Bermudez M, Wolber G2. Structure versus function—The impact of computational methods on the discovery of specific GPCR-ligands. Bioorg Med Chem 2015.23(14):3907-12
  • Ngo T, Finch A, Griffith R. Structure-based drug design and drug discovery for G protein-coupled receptors. Austral Biochem 2013;44(2):4-6.12
  • 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(4):1088-97
  • Hu J, Wang Y, Zhang X, et al. Structural basis of G protein-coupled receptor-G protein interactions. Nat Chem Biol 2010;6:541-8
  • Koschatzky S, Tschammer N, Gmeine P. Cross-receptor interactions between dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics. ACS Chem Neurosci 2011;2:308-16
  • Beuming T, Sherman W. Current Assessment of docking into GPCR crystal structures and homology models: successes, challenges, and guidelines. J Chem Inf Model 2012;52:3263-77
  • McRobb FM, Crosby IT, Yuriev E, et al. Homobivalent ligands of the atypical antipsychotic clozapine: design, synthesis, and pharmacological evaluation. J Med Chem 2012;55(4):1622-34
  • Choi WT, Kumar S, Madani N, et al. A novel synthetic bivalent ligand to probe chemokine receptor CXCR4 dimerization and inhibit HIV-1 entry. Biochemistry 2012;51(36):7078-86
  • Congreve M, Dias JM, Marshall FH. Structure-based drug design for G protein-coupled receptors. Prog Med Chem 2014;53:1-63
  • Congreve M, Langmead CJ, Mason JS, et al. Progress in structure based drug design for G protein-coupled receptors. J Med Chem 2011;54(13):4283-311
  • Receptos. Receptos reports positive phase 2 results for RPC1063 in relapsing multiple sclerosis. Available from: http://ir.receptos.com/releasedetail.cfm?releaseid=853628 [Report dated 9 June 2014]
  • Kruse AC, Ring AM, Manglik A, et al. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature 2013;504:101-6
  • Bernstein FC, Koetzle TF, Williams GJ, et al. The protein data bank: A computer-based archival file for macromolecular structures. J Mol Biol 1977;112(3):535-42
  • Excel 2013; 640 8th Avenue, New York, NY 10019
  • Schrödinger Release 2014-2: Maestro, version 9.8, Schrödinger, LLC, New York, NY, 2014

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