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Y.; Karschin, A.; Branchek, T.; Davidson, N.; Lester, H. A. The role of conserved aspartate and serine residues in ligand binding and in function of the 5-HT1A receptor: a site-directed mutation study. FEBS Lett. 1992, 312, 259−62. (42) Javitch, J. A.; Ballesteros, J. A.; 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. (43) Prandi, A.; Franchini, S.; Manasieva, L. I.; Fossa, P.; Cichero, E.; Marucci, G.; Buccioni, M.; Cilia, A.; Pirona, L.; Brasili, L. Synthesis, biological evaluation, and docking studies of tetrahydrofuran￾cyclopentanone- and cyclopentanol-based ligands acting at adrenergic alpha(1)- and serotonine 5-HT1A receptors. J. Med. Chem. 2012, 55, 23−36. (44) Nowak, M.; Kolaczkowski, M.; Pawlowski, M.; Bojarski, A. J. Homology modeling of the serotonin 5-HT1A receptor using automated docking of bioactive compounds with defined geometry. J. Med. Chem. 2006, 49, 205−14. (45) Gü ner, O. F.; Henry, D. R. Metrics for Analyzing Hit Lists and Pharmacophores. In Pharmacophore Perception, Development, and Use for Drug Design; International University Line: 2000; pp 193−211. (46) Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B.; Overington, J. P. ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012, 40, D1100−7. (47) Mysinger, M. M.; Carchia, M.; Irwin, J. J.; Shoichet, B. K. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking. J. Med. Chem. 2012, 55, 6582−6594. (48) Rasmussen, S. G. F.; 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 [bgr]2 adrenoceptor. Nature 2011, 469, 175−180. (49) Schwartz, T. W.; Frimurer, T. M.; Holst, B.; Rosenkilde, M. M.; Elling, C. E. Molecular mechanism of 7TM receptor activation–a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 2006, 46, 481−519. (50) Katritch, V.; Cherezov, V.; Stevens, R. C. Structure-function of the G protein-coupled receptor superfamily. Annu. Rev. Pharmacol. Toxicol. 2013, 53, 531−56. (51) Chanda, P. K.; Minchin, M. C.; Davis, A. R.; Greenberg, L.; Reilly, Y.; McGregor, W. H.; Bhat, R.; Lubeck, M. D.; Mizutani, S.; Hung, P. P. Identification of residues important for ligand binding to the human 5-hydroxytryptamine1A serotonin receptor. Mol. Pharma￾col. 1993, 43, 516−20. (52) Liapakis, G.; Ballesteros, J. A.; Papachristou, S.; Chan, W. C.; Chen, X.; Javitch, J. A. The forgotten serine: a critical role for Ser- 2035.42 in ligand binding to and activation of the β2-adrenergic receptor. J. Biol. Chem. 2000, 275, 37779−37788. (53) 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, 40989−96. Journal of Chemical Information and Modeling Article 3211 dx.doi.org/10.1021/ci400481p | J. Chem. Inf. Model. 2013, 53, 3202−3211