eprintid: 10185650 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/18/56/50 datestamp: 2024-01-18 11:51:28 lastmod: 2024-12-28 07:10:07 status_changed: 2024-01-18 11:51:28 type: article metadata_visibility: show sword_depositor: 699 creators_name: Calderón, Jacqueline C creators_name: Plut, Eva creators_name: Keller, Max creators_name: Cabrele, Chiara creators_name: Reiser, Oliver creators_name: Gervasio, Francesco L creators_name: Clark, Timothy title: Extended Metadynamics Protocol for Binding/Unbinding Free Energies of Peptide Ligands to Class A G-Protein-Coupled Receptors ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F56 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: A metadynamics protocol is presented to characterize the binding and unbinding of peptide ligands to class A G-protein-coupled receptors (GPCRs). The protocol expands on the one previously presented for binding and unbinding small-molecule ligands to class A GPCRs and accounts for the more demanding nature of the peptide binding-unbinding process. It applies to almost all class A GPCRs. Exemplary simulations are described for subtypes Y1R, Y2R, and Y4R of the neuropeptide Y receptor family, vasopressin binding to the vasopressin V2 receptor (V2R), and oxytocin binding to the oxytocin receptor (OTR). Binding free energies and the positions of alternative binding sites are presented and, where possible, compared with the experiment. date: 2024-01-08 date_type: published publisher: American Chemical Society official_url: https://doi.org/10.1021/acs.jcim.3c01574 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2137904 doi: 10.1021/acs.jcim.3c01574 medium: Print-Electronic lyricists_name: Gervasio, Francesco Luigi lyricists_id: FLGER36 actors_name: Gervasio, Francesco Luigi actors_id: FLGER36 actors_role: owner full_text_status: public publication: Journal of Chemical Information and Modeling volume: 64 number: 1 pagerange: 205-218 event_location: United States issn: 1549-9596 citation: Calderón, Jacqueline C; Plut, Eva; Keller, Max; Cabrele, Chiara; Reiser, Oliver; Gervasio, Francesco L; Clark, Timothy; (2024) Extended Metadynamics Protocol for Binding/Unbinding Free Energies of Peptide Ligands to Class A G-Protein-Coupled Receptors. Journal of Chemical Information and Modeling , 64 (1) pp. 205-218. 10.1021/acs.jcim.3c01574 <https://doi.org/10.1021/acs.jcim.3c01574>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10185650/1/accepted.pdf