Extended Metadynamics Protocol for Binding/Unbinding Free Energies of Peptide Ligands to Class A G-Protein-Coupled Receptors

Calderón JC, Plut E, Keller M, Cabrele C, Reiser O, Gervasio FL, Clark T (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Chemical Information and Modeling American Chemical Society

Book Volume: 64

Pages Range: 205-218

Journal Issue: 1

DOI: 10.1021/acs.jcim.3c01574

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.

Authors with CRIS profile

Timothy Clark Computer-Chemie-Centrum

Involved external institutions

Universität Regensburg DE Germany (DE) University of Geneva / Université de Genève (UNIGE) CH Switzerland (CH)

How to cite

APA:

Calderón, J.C., Plut, E., Keller, M., Cabrele, C., Reiser, O., Gervasio, F.L., & Clark, T. (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), 205-218. https://doi.org/10.1021/acs.jcim.3c01574

MLA:

Calderón, Jacqueline C., et al. "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 (2024): 205-218.

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