{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:12Z","timestamp":1792790352555,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Biophysics","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH Common Fund","award":["1R01GM149659"],"award-info":[{"award-number":["1R01GM149659"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH Common Fund","award":["1R21ES035378"],"award-info":[{"award-number":["1R21ES035378"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  G protein-coupled receptors (GPCRs) represent the largest membrane protein family in the human body and the major targets of FDA-approved medications. Unlike some other physiological proteins, GPCRs are highly plastic and often exist as collections of conformational ensembles in the environment to exert their function. Therefore, understanding how a GPCR adopts different conformational ensembles in response to ligands and signaling partners is essential for drug development.\n                  <jats:sup>19<\/jats:sup>\n                  F-NMR has emerged as one of the most promising tools in this regard; however, a well-established\n                  <jats:sup>19<\/jats:sup>\n                  F-labeling system is still lacking, including an effective\n                  <jats:sup>19<\/jats:sup>\n                  F probe that meets both environmental susceptibility and NMR sensitivity requirements, even though progress has been made dramatically in recent years. Thus, this manuscript reports a novel conformational probe (4-(bromomethyl)- ethoxy-2-(trifluoromethyl)benzene, BTMB) that offers paramount benefits for future GPCR conformational dynamics studies. To rationalize the mechanism behind BTMB\u2019s superiority for future probe development, we performed MD simulations, referenced to the current state-of-the-art probe, BTFMA. Our study suggests that the spatial proximity of aromatic residues significantly influences the chemical shift dispersion and linewidths of related\n                  <jats:sup>19<\/jats:sup>\n                  F-probe-profiled conformational states, as well as the rigidity and compactness of -CF\n                  <jats:sub>3<\/jats:sub>\n                  in the target protein.\n                <\/jats:p>","DOI":"10.64898\/2026.09.18.752616","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:10:17Z","timestamp":1790262617000},"source":"Crossref","is-referenced-by-count":0,"title":["An Excelled Trifluorinated Probe for GPCR Conformational Quantification"],"prefix":"10.64898","author":[{"given":"Xudong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL, USA 60208;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0818-2972","authenticated-orcid":false,"given":"Libin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA 33620"},{"name":"H. 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