TY - JOUR SP - 205 UR - https://doi.org/10.1021/acs.jcim.3c01574 TI - Extended Metadynamics Protocol for Binding/Unbinding Free Energies of Peptide Ligands to Class A G-Protein-Coupled Receptors ID - discovery10185650 SN - 1549-9596 N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. EP - 218 JF - Journal of Chemical Information and Modeling AV - public N2 - 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. VL - 64 IS - 1 A1 - Calderón, Jacqueline C A1 - Plut, Eva A1 - Keller, Max A1 - Cabrele, Chiara A1 - Reiser, Oliver A1 - Gervasio, Francesco L A1 - Clark, Timothy Y1 - 2024/01/08/ PB - American Chemical Society ER -