{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:27:53Z","timestamp":1791379673085,"version":"4.3.3"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T00:00:00Z","timestamp":1512950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Chem Biol"],"published-print":{"date-parts":[[2018,2]]},"DOI":"10.1038\/nchembio.2527","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T16:02:54Z","timestamp":1513008174000},"page":"126-134","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Structure-inspired design of \u03b2-arrestin-biased ligands for aminergic GPCRs"],"prefix":"10.1038","volume":"14","author":[{"given":"John D","family":"McCorvy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle V","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Rechsteiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Karpiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M","family":"Betz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany L","family":"Kormos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K","family":"Shoichet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron O","family":"Dror","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-3862","authenticated-orcid":false,"given":"Jian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,11]]},"reference":[{"key":"BFnchembio2527_CR1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/nrd2199","volume":"5","author":"JP Overington","year":"2006","unstructured":"Overington, J.P., Al-Lazikani, B. & Hopkins, A.L. How many drug targets are there? Nat. Rev. Drug Discov. 5, 993\u2013996 (2006).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnchembio2527_CR2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrd3478","volume":"10","author":"M Rask-Andersen","year":"2011","unstructured":"Rask-Andersen, M., Alm\u00e9n, M.S. & Schi\u00f6th, H.B. Trends in the exploitation of novel drug targets. Nat. Rev. Drug Discov. 10, 579\u2013590 (2011).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnchembio2527_CR3","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cell.2017.07.009","volume":"170","author":"D Wacker","year":"2017","unstructured":"Wacker, D., Stevens, R.C. & Roth, B.L. How ligands illuminate GPCR molecular pharmacology. Cell 170, 414\u2013427 (2017).","journal-title":"Cell"},{"key":"BFnchembio2527_CR4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.106.104463","volume":"320","author":"JD Urban","year":"2007","unstructured":"Urban, J.D. et al. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. 320, 1\u201313 (2007).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFnchembio2527_CR5","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.physiol.69.022405.154749","volume":"69","author":"SM DeWire","year":"2007","unstructured":"DeWire, S.M., Ahn, S., Lefkowitz, R.J. & Shenoy, S.K. \u03b2-arrestins and cell signaling. Annu. Rev. Physiol. 69, 483\u2013510 (2007).","journal-title":"Annu. Rev. Physiol."},{"key":"BFnchembio2527_CR6","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.tibs.2011.06.003","volume":"36","author":"AK Shukla","year":"2011","unstructured":"Shukla, A.K., Xiao, K. & Lefkowitz, R.J. Emerging paradigms of \u03b2-arrestin-dependent seven transmembrane receptor signaling. Trends Biochem. Sci. 36, 457\u2013469 (2011).","journal-title":"Trends Biochem. Sci."},{"key":"BFnchembio2527_CR7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.tips.2014.04.007","volume":"35","author":"JD Violin","year":"2014","unstructured":"Violin, J.D., Crombie, A.L., Soergel, D.G. & Lark, M.W. Biased ligands at G-protein-coupled receptors: promise and progress. Trends Pharmacol. Sci. 35, 308\u2013316 (2014).","journal-title":"Trends Pharmacol. Sci."},{"key":"BFnchembio2527_CR8","doi-asserted-by":"crossref","first-page":"18488","DOI":"10.1073\/pnas.1104807108","volume":"108","author":"JA Allen","year":"2011","unstructured":"Allen, J.A. et al. Discovery of \u03b2-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc. Natl. Acad. Sci. USA 108, 18488\u201318493 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio2527_CR9","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.pain.2014.06.011","volume":"155","author":"DG Soergel","year":"2014","unstructured":"Soergel, D.G. et al. Biased agonism of the \u03bc-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Pain 155, 1829\u20131835 (2014).","journal-title":"Pain"},{"key":"BFnchembio2527_CR10","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1124\/jpet.110.173005","volume":"335","author":"JD Violin","year":"2010","unstructured":"Violin, J.D. et al. Selectively engaging \u03b2-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance. J. Pharmacol. Exp. Ther. 335, 572\u2013579 (2010).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFnchembio2527_CR11","doi-asserted-by":"crossref","first-page":"E2517","DOI":"10.1073\/pnas.1502740112","volume":"112","author":"NM Urs","year":"2015","unstructured":"Urs, N.M. et al. Targeting \u03b2-arrestin2 in the treatment of L-DOPA-induced dyskinesia in Parkinson's disease. Proc. Natl. Acad. Sci. USA 112, E2517\u2013E2526 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio2527_CR12","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/bph.12705","volume":"172","author":"I Charfi","year":"2015","unstructured":"Charfi, I., Audet, N., Bagheri Tudashki, H. & Pineyro, G. Identifying ligand-specific signalling within biased responses: focus on \u03b4 opioid receptor ligands. Br. J. Pharmacol. 172, 435\u2013448 (2015).","journal-title":"Br. J. Pharmacol."},{"key":"BFnchembio2527_CR13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature19112","volume":"537","author":"A Manglik","year":"2016","unstructured":"Manglik, A. et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature 537, 185\u2013190 (2016).","journal-title":"Nature"},{"key":"BFnchembio2527_CR14","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1124\/jpet.112.201616","volume":"344","author":"SM DeWire","year":"2013","unstructured":"DeWire, S.M. et al. A G protein-biased ligand at the \u03bc-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J. Pharmacol. Exp. Ther. 344, 708\u2013717 (2013).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFnchembio2527_CR15","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1210\/me.2012-1091","volume":"27","author":"D Gesty-Palmer","year":"2013","unstructured":"Gesty-Palmer, D. et al. \u03b2-arrestin-selective G protein-coupled receptor agonists engender unique biological efficacy in vivo. Mol. Endocrinol. 27, 296\u2013314 (2013).","journal-title":"Mol. Endocrinol."},{"key":"BFnchembio2527_CR16","doi-asserted-by":"crossref","first-page":"13656","DOI":"10.1073\/pnas.0803522105","volume":"105","author":"B Masri","year":"2008","unstructured":"Masri, B. et al. Antagonism of dopamine D2 receptor\/\u03b2-arrestin 2 interaction is a common property of clinically effective antipsychotics. Proc. Natl. Acad. Sci. USA 105, 13656\u201313661 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio2527_CR17","doi-asserted-by":"crossref","first-page":"22255","DOI":"10.1073\/pnas.1009633108","volume":"107","author":"B Tchernychev","year":"2010","unstructured":"Tchernychev, B. et al. Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells. Proc. Natl. Acad. Sci. USA 107, 22255\u201322259 (2010).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnchembio2527_CR18","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1126\/science.1150577","volume":"318","author":"V Cherezov","year":"2007","unstructured":"Cherezov, V. et al. High-resolution crystal structure of an engineered human \u03b22-adrenergic G protein-coupled receptor. Science 318, 1258\u20131265 (2007).","journal-title":"Science"},{"key":"BFnchembio2527_CR19","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1126\/science.1197410","volume":"330","author":"EY Chien","year":"2010","unstructured":"Chien, E.Y. et al. Structure of the human dopamine D3 receptor in complex with a D2\/D3 selective antagonist. Science 330, 1091\u20131095 (2010).","journal-title":"Science"},{"key":"BFnchembio2527_CR20","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature10361","volume":"477","author":"SG Rasmussen","year":"2011","unstructured":"Rasmussen, S.G. et al. Crystal structure of the \u03b22 adrenergic receptor-Gs protein complex. Nature 477, 549\u2013555 (2011).","journal-title":"Nature"},{"key":"BFnchembio2527_CR21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature12572","volume":"502","author":"AM Ring","year":"2013","unstructured":"Ring, A.M. et al. Adrenaline-activated structure of \u03b22-adrenoceptor stabilized by an engineered nanobody. Nature 502, 575\u2013579 (2013).","journal-title":"Nature"},{"key":"BFnchembio2527_CR22","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1126\/science.1232808","volume":"340","author":"D Wacker","year":"2013","unstructured":"Wacker, D. et al. Structural features for functional selectivity at serotonin receptors. Science 340, 615\u2013619 (2013).","journal-title":"Science"},{"key":"BFnchembio2527_CR23","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1126\/science.1232807","volume":"340","author":"C Wang","year":"2013","unstructured":"Wang, C. et al. Structural basis for molecular recognition at serotonin receptors. Science 340, 610\u2013614 (2013).","journal-title":"Science"},{"key":"BFnchembio2527_CR24","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev.med.52.1.503","volume":"52","author":"S Kapur","year":"2001","unstructured":"Kapur, S. & Remington, G. Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia. Annu. Rev. Med. 52, 503\u2013517 (2001).","journal-title":"Annu. Rev. Med."},{"key":"BFnchembio2527_CR25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0893-133X(01)00261-5","volume":"25","author":"ML Wadenberg","year":"2001","unstructured":"Wadenberg, M.L., Soliman, A., VanderSpek, S.C. & Kapur, S. Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects. Neuropsychopharmacology 25, 633\u2013641 (2001).","journal-title":"Neuropsychopharmacology"},{"key":"BFnchembio2527_CR26","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/sj.npp.1300203","volume":"28","author":"DA Shapiro","year":"2003","unstructured":"Shapiro, D.A. et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 28, 1400\u20131411 (2003).","journal-title":"Neuropsychopharmacology"},{"key":"BFnchembio2527_CR27","doi-asserted-by":"crossref","first-page":"10601","DOI":"10.1021\/acs.jmedchem.6b01208","volume":"59","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. Discovery of G protein-biased D2 dopamine receptor partial agonists. J. Med. Chem. 59, 10601\u201310618 (2016).","journal-title":"J. Med. Chem."},{"key":"BFnchembio2527_CR28","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/npp.2015.196","volume":"41","author":"SM Park","year":"2016","unstructured":"Park, S.M. et al. Effects of \u03b2-arrestin-biased dopamine D2 receptor ligands on schizophrenia-like behavior in hypoglutamatergic mice. Neuropsychopharmacology 41, 704\u2013715 (2016).","journal-title":"Neuropsychopharmacology"},{"key":"BFnchembio2527_CR29","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0026-895X(24)26458-0","volume":"57","author":"C Ambrosio","year":"2000","unstructured":"Ambrosio, C., Molinari, P., Cotecchia, S. & Costa, T. Catechol-binding serines of \u03b22-adrenergic receptors control the equilibrium between active and inactive receptor states. Mol. Pharmacol. 57, 198\u2013210 (2000).","journal-title":"Mol. Pharmacol."},{"key":"BFnchembio2527_CR30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature16577","volume":"530","author":"S Isogai","year":"2016","unstructured":"Isogai, S. et al. Backbone NMR reveals allosteric signal transduction networks in the \u03b21-adrenergic receptor. Nature 530, 237\u2013241 (2016).","journal-title":"Nature"},{"key":"BFnchembio2527_CR31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature09746","volume":"469","author":"T Warne","year":"2011","unstructured":"Warne, T. et al. The structural basis for agonist and partial agonist action on a \u03b21-adrenergic receptor. Nature 469, 241\u2013244 (2011).","journal-title":"Nature"},{"key":"BFnchembio2527_CR32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1042\/bst0230112","volume":"23","author":"KA Neve","year":"1995","unstructured":"Neve, K.A. & Wiens, B.L. Four ways of being an agonist: multiple sequence determinants of efficacy at D2 dopamine receptors. Biochem. Soc. Trans. 23, 112\u2013116 (1995).","journal-title":"Biochem. Soc. Trans."},{"key":"BFnchembio2527_CR33","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1124\/mol.54.2.435","volume":"54","author":"BL Wiens","year":"1998","unstructured":"Wiens, B.L., Nelson, C.S. & Neve, K.A. Contribution of serine residues to constitutive and agonist-induced signaling via the D2S dopamine receptor: evidence for multiple, agonist-specific active conformations. Mol. Pharmacol. 54, 435\u2013444 (1998).","journal-title":"Mol. Pharmacol."},{"key":"BFnchembio2527_CR34","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1124\/mol.111.075457","volume":"81","author":"JC Fowler","year":"2012","unstructured":"Fowler, J.C., Bhattacharya, S., Urban, J.D., Vaidehi, N. & Mailman, R.B. Receptor conformations involved in dopamine D(2L) receptor functional selectivity induced by selected transmembrane-5 serine mutations. Mol. Pharmacol. 81, 820\u2013831 (2012).","journal-title":"Mol. Pharmacol."},{"key":"BFnchembio2527_CR35","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cell.2016.12.033","volume":"168","author":"D Wacker","year":"2017","unstructured":"Wacker, D. et al. Crystal structure of an LSD-bound human serotonin receptor. Cell 168, 377\u2013389.e12 (2017).","journal-title":"Cell"},{"key":"BFnchembio2527_CR36","doi-asserted-by":"crossref","first-page":"7141","DOI":"10.1021\/jm300603y","volume":"55","author":"X Chen","year":"2012","unstructured":"Chen, X. et al. Structure-functional selectivity relationship studies of \u03b2-arrestin-biased dopamine D2 receptor agonists. J. Med. Chem. 55, 7141\u20137153 (2012).","journal-title":"J. Med. Chem."},{"key":"BFnchembio2527_CR37","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1021\/jm400140q","volume":"56","author":"JA Christopher","year":"2013","unstructured":"Christopher, J.A. et al. Biophysical fragment screening of the \u03b21-adrenergic receptor: identification of high affinity arylpiperazine leads using structure-based drug design. J. Med. Chem. 56, 3446\u20133455 (2013).","journal-title":"J. Med. Chem."},{"key":"BFnchembio2527_CR38","doi-asserted-by":"crossref","first-page":"e100069","DOI":"10.1371\/journal.pone.0100069","volume":"9","author":"RC Kling","year":"2014","unstructured":"Kling, R.C., Tschammer, N., Lanig, H., Clark, T. & Gmeiner, P. Active-state model of a dopamine D2 receptor-G\u03b1i complex stabilized by aripiprazole-type partial agonists. PLoS One 9, e100069 (2014).","journal-title":"PLoS One"},{"key":"BFnchembio2527_CR39","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1021\/cn300142q","volume":"3","author":"RR Luedtke","year":"2012","unstructured":"Luedtke, R.R. et al. Comparison of the binding and functional properties of two structurally different D2 dopamine receptor subtype selective compounds. ACS Chem. Neurosci. 3, 1050\u20131062 (2012).","journal-title":"ACS Chem. Neurosci."},{"key":"BFnchembio2527_CR40","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nsmb.3014","volume":"22","author":"WK Kroeze","year":"2015","unstructured":"Kroeze, W.K. et al. PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome. Nat. Struct. Mol. Biol. 22, 362\u2013369 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFnchembio2527_CR41","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1038\/ncomms10842","volume":"7","author":"C Klein Herenbrink","year":"2016","unstructured":"Klein Herenbrink, C. et al. The role of kinetic context in apparent biased agonism at GPCRs. Nat. Commun. 7, 10842 (2016).","journal-title":"Nat. Commun."},{"key":"BFnchembio2527_CR42","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nsmb.1549","volume":"16","author":"S Ahuja","year":"2009","unstructured":"Ahuja, S. et al. Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation. Nat. Struct. Mol. Biol. 16, 168\u2013175 (2009).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFnchembio2527_CR43","doi-asserted-by":"crossref","first-page":"15245","DOI":"10.1021\/bi026444k","volume":"41","author":"S Kuwayama","year":"2002","unstructured":"Kuwayama, S., Imai, H., Hirano, T., Terakita, A. & Shichida, Y. Conserved proline residue at position 189 in cone visual pigments as a determinant of molecular properties different from rhodopsins. Biochemistry 41, 15245\u201315252 (2002).","journal-title":"Biochemistry"},{"key":"BFnchembio2527_CR44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1042\/BST20120228","volume":"41","author":"T Warne","year":"2013","unstructured":"Warne, T. & Tate, C.G. The importance of interactions with helix 5 in determining the efficacy of \u03b2-adrenoceptor ligands. Biochem. Soc. Trans. 41, 159\u2013165 (2013).","journal-title":"Biochem. Soc. Trans."},{"key":"BFnchembio2527_CR45","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.sbi.2011.06.002","volume":"21","author":"X Deupi","year":"2011","unstructured":"Deupi, X. & Standfuss, J. Structural insights into agonist-induced activation of G-protein-coupled receptors. Curr. Opin. Struct. Biol. 21, 541\u2013551 (2011).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"BFnchembio2527_CR46","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrd1346","volume":"3","author":"BL Roth","year":"2004","unstructured":"Roth, B.L., Sheffler, D.J. & Kroeze, W.K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov. 3, 353\u2013359 (2004).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnchembio2527_CR47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature11691","volume":"492","author":"J Besnard","year":"2012","unstructured":"Besnard, J. et al. Automated design of ligands to polypharmacological profiles. Nature 492, 215\u2013220 (2012).","journal-title":"Nature"},{"key":"BFnchembio2527_CR48","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nature14886","volume":"524","author":"W Huang","year":"2015","unstructured":"Huang, W. et al. Structural insights into \u03bc-opioid receptor activation. Nature 524, 315\u2013321 (2015).","journal-title":"Nature"},{"key":"BFnchembio2527_CR49","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.tips.2007.11.009","volume":"29","author":"B Kobilka","year":"2008","unstructured":"Kobilka, B. & Schertler, G.F. New G-protein-coupled receptor crystal structures: insights and limitations. Trends Pharmacol. Sci. 29, 79\u201383 (2008).","journal-title":"Trends Pharmacol. Sci."},{"key":"BFnchembio2527_CR50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0026-895X(25)15016-5","volume":"25","author":"HJ Motulsky","year":"1984","unstructured":"Motulsky, H.J. & Mahan, L.C. The kinetics of competitive radioligand binding predicted by the law of mass action. Mol. Pharmacol. 25, 1\u20139 (1984).","journal-title":"Mol. Pharmacol."},{"key":"BFnchembio2527_CR51","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1021\/cn200111m","volume":"3","author":"T Kenakin","year":"2012","unstructured":"Kenakin, T., et al. A simple method for quantifying functional selectivity and agonist bias. ACS Chem. Neurosci. 3, 193\u2013203 (2012).","journal-title":"ACS Chem. Neurosci."},{"key":"BFnchembio2527_CR52","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1021\/cb400103f","volume":"8","author":"DR Weiss","year":"2013","unstructured":"Weiss, D.R. et al. Conformation guides molecular efficacy in docking screens of activated \u03b2-2 adrenergic G protein coupled receptor. ACS Chem. Biol. 8, 1018\u20131026 (2013).","journal-title":"ACS Chem. Biol."},{"key":"BFnchembio2527_CR53","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10822-014-9722-6","volume":"28","author":"RG Coleman","year":"2014","unstructured":"Coleman, R.G., Sterling, T. & Weiss, D.R. SAMPL4 & DOCK3.7: lessons for automated docking procedures. J. Comput. Aided Mol. Des. 28, 201\u2013209 (2014).","journal-title":"J. Comput. Aided Mol. Des."},{"key":"BFnchembio2527_CR54","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/bioinformatics\/btk023","volume":"22","author":"MA Lomize","year":"2006","unstructured":"Lomize, M.A., Lomize, A.L., Pogozheva, I.D. & Mosberg, H.I. OPM: orientations of proteins in membranes database. Bioinformatics 22, 623\u2013625 (2006).","journal-title":"Bioinformatics"},{"key":"BFnchembio2527_CR55","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/(SICI)1097-0134(199604)24:4<433::AID-PROT3>3.0.CO;2-F","volume":"24","author":"L Zhang","year":"1996","unstructured":"Zhang, L. & Hermans, J. Hydrophilicity of cavities in proteins. Proteins 24, 433\u2013438 (1996).","journal-title":"Proteins"},{"key":"BFnchembio2527_CR56","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/ct300400x","volume":"8","author":"RB Best","year":"2012","unstructured":"Best, R.B. et al. Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone \u03d5, \u03c8 and side-chain \u03c7(1) and \u03c7(2) dihedral angles. J. Chem. Theory Comput. 8, 3257\u20133273 (2012).","journal-title":"J. Chem. Theory Comput."},{"key":"BFnchembio2527_CR57","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1021\/ci300363c","volume":"52","author":"K Vanommeslaeghe","year":"2012","unstructured":"Vanommeslaeghe, K. & MacKerell, A.D. Jr. Automation of the CHARMM general force field (CGenFF) I: bond perception and atom typing. J. Chem. Inf. Model. 52, 3144\u20133154 (2012).","journal-title":"J. Chem. Inf. Model."},{"key":"BFnchembio2527_CR58","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jcc.23775","volume":"36","author":"RM Betz","year":"2015","unstructured":"Betz, R.M. & Walker, R.C. Paramfit: automated optimization of force field parameters for molecular dynamics simulations. J. Comput. Chem. 36, 79\u201387 (2015).","journal-title":"J. Comput. Chem."},{"key":"BFnchembio2527_CR59","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","volume":"9","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer, R., G\u00f6tz, A.W., Poole, D., Le Grand, S. & Walker, R.C. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh ewald. J. Chem. Theory Comput. 9, 3878\u20133888 (2013).","journal-title":"J. Chem. Theory Comput."},{"key":"BFnchembio2527_CR60","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33\u201338 (1996).","journal-title":"J. Mol. Graph."},{"key":"BFnchembio2527_CR61","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","volume":"9","author":"DR Roe","year":"2013","unstructured":"Roe, D.R. & Cheatham, T.E. III. PTRAJ and CPPTRAJ: software for processing and analysis of molecular synamics trajectory data. J. Chem. Theory Comput. 9, 3084\u20133095 (2013).","journal-title":"J. Chem. Theory Comput."}],"container-title":["Nature Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nchembio.2527.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nchembio.2527","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nchembio.2527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nchembio.2527.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T13:43:56Z","timestamp":1751118236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nchembio.2527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,11]]},"references-count":61,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["BFnchembio2527"],"URL":"https:\/\/doi.org\/10.1038\/nchembio.2527","relation":{},"ISSN":["1552-4450","1552-4469"],"issn-type":[{"value":"1552-4450","type":"print"},{"value":"1552-4469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,11]]},"assertion":[{"value":"20 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}