posted on 2023-12-27, 18:06authored byJacqueline
C. Calderón, Eva Plut, Max Keller, Chiara Cabrele, Oliver Reiser, Francesco L. Gervasio, Timothy Clark
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.