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Biol."},{"key":"10.1016\/j.cell.2025.10.034_bib77","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cardiores.2005.08.004","article-title":"Evidence that inward rectifier K+ channels mediate relaxation by the PGI2 receptor agonist cicaprost via a cyclic AMP-independent mechanism","volume":"69","author":"Orie","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.cell.2025.10.034_bib78","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/nmeth.2172","article-title":"TGF\u03b1 shedding assay: an accurate and versatile method for detecting GPCR activation","volume":"9","author":"Inoue","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cell.2025.10.034_bib79","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.4193","article-title":"MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy","volume":"14","author":"Zheng","year":"2017","journal-title":"Nat. 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Des."},{"key":"10.1016\/j.cell.2025.10.034_bib86","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.cell.2025.10.034_bib87","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein\u2212Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.cell.2025.10.034_bib88","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. 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Chem."},{"key":"10.1016\/j.cell.2025.10.034_bib97","doi-asserted-by":"crossref","first-page":"D370","DOI":"10.1093\/nar\/gkr703","article-title":"OPM database and PPM web server: resources for positioning of proteins in membranes","volume":"40","author":"Lomize","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2025.10.034_bib98","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acs.jctc.5b00935","article-title":"CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM\/OpenMM Simulations Using the CHARMM36 Additive Force Field","volume":"12","author":"Lee","year":"2016","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.cell.2025.10.034_bib99","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: an improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. 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