{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:31:41Z","timestamp":1792045901071,"version":"4.4.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971153"],"award-info":[{"award-number":["31971153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670733"],"award-info":[{"award-number":["31670733"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21904088"],"award-info":[{"award-number":["21904088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,4,12]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    G protein-coupled receptor (GPCR) structures determined by X-ray crystallography or cryo-electron microscopy include 28 receptors for which complexes with agonists and antagonists can be compared. In all these comparisons, an interatomic distance representing the size of the orthosteric ligand binding groove differs by less than 2.9 \u00c5. In this report,\n                    <jats:sup>19<\/jats:sup>\n                    F-NMR observations of the NK1R-bound drug molecule aprepitant show that the orthosteric binding groove undergoes transient fluctuations with amplitudes 6 to 8 \u00c5. We propose that this large-amplitude plasticity enables a multistep selection of functional ligands with variable efficacies. These insights into structural dynamics also provide a rationale for the observation that diffracting crystals are obtained for GPCR complexes with only few of the ligands that bind to the receptors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2122682119","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T15:27:16Z","timestamp":1649086036000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["GPCR large-amplitude dynamics by\n                    <sup>19<\/sup>\n                    F-NMR of aprepitant bound to the neurokinin 1 receptor"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-1706","authenticated-orcid":false,"given":"Benxun","family":"Pan","sequence":"first","affiliation":[{"name":"iHuman Institute, ShanghaiTech University, Shanghai 201210, China"},{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China"},{"name":"Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2053-1752","authenticated-orcid":false,"given":"Dongsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"iHuman Institute, ShanghaiTech University, Shanghai 201210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0915-7744","authenticated-orcid":false,"given":"Lingyun","family":"Yang","sequence":"additional","affiliation":[{"name":"iHuman Institute, ShanghaiTech University, Shanghai 201210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"iHuman Institute, ShanghaiTech University, Shanghai 201210, China"},{"name":"Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1640"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb33114.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00890-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2013"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm980299k"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1200\/JCO.2003.01.095","article-title":"The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin\u2014The Aprepitant Protocol 052 Study Group","volume":"21","author":"Hesketh P. 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