Lopez-Balastegui, MartaStepniewski, Tomasz Maciej, 1988-Kogut-Günthel, Małgorzata M.Di Pizio, AntonellaRosenkilde, Mette MarieMao, JiafeiSelent, Jana2025-03-102025-03-102024Lopez-Balastegui M, Stepniewski TM, Kogut-Günthel MM, Di Pizio A, Rosenkilde MM, Mao J, et al. Relevance of G protein-coupled receptor (GPCR) dynamics for receptor activation, signalling bias and allosteric modulation. Br J Pharmacol. 2024 Jul 8. DOI: 10.1111/bph.164950007-1188http://hdl.handle.net/10230/69884Data de publicació electrònica: 08-07-2024G protein-coupled receptors (GPCRs) are one of the major drug targets. In recent years, computational drug design for GPCRs has mainly focused on static structures obtained through X-ray crystallography, cryogenic electron microscopy (cryo-EM) or in silico modelling as a starting point for virtual screening campaigns. However, GPCRs are highly flexible entities with the ability to adopt different conformational states that elicit different physiological responses. Including this knowledge in the drug discovery pipeline can help to tailor novel conformation-specific drugs with an improved therapeutic profile. In this review, we outline our current knowledge about GPCR dynamics that is relevant for receptor activation, signalling bias and allosteric modulation. Ultimately, we highlight new technological implementations such as time-resolved X-ray crystallography and cryo-EM as well as computational algorithms that can contribute to a more comprehensive understanding of receptor dynamics and its relevance for GPCR functionality.application/pdfeng© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/bph.16495Allosteric modulationDrug designGPCR dynamicsMolecular dynamics simulationsSignalling biasTime‐resolved experimental techniquesinfo:eu-repo/semantics/openAccess