Relevance of G protein-coupled receptor (GPCR) dynamics for receptor activation, signalling bias and allosteric modulation
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- dc.contributor.author Lopez-Balastegui, Marta
- dc.contributor.author Stepniewski, Tomasz Maciej, 1988-
- dc.contributor.author Kogut-Günthel, Małgorzata M.
- dc.contributor.author Di Pizio, Antonella
- dc.contributor.author Rosenkilde, Mette Marie
- dc.contributor.author Mao, Jiafei
- dc.contributor.author Selent, Jana
- dc.date.accessioned 2025-03-10T06:55:56Z
- dc.date.available 2025-03-10T06:55:56Z
- dc.date.issued 2024
- dc.description Data de publicació electrònica: 08-07-2024
- dc.description.abstract G 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Lopez-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.16495
- dc.identifier.doi http://dx.doi.org/10.1111/bph.16495
- dc.identifier.issn 0007-1188
- dc.identifier.uri http://hdl.handle.net/10230/69884
- dc.language.iso eng
- dc.publisher Wiley
- dc.relation.ispartof Br J Pharmacol. 2024 Jul 8
- dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101080465
- dc.rights © 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.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Allosteric modulation
- dc.subject.keyword Drug design
- dc.subject.keyword GPCR dynamics
- dc.subject.keyword Molecular dynamics simulations
- dc.subject.keyword Signalling bias
- dc.subject.keyword Time‐resolved experimental techniques
- dc.title Relevance of G protein-coupled receptor (GPCR) dynamics for receptor activation, signalling bias and allosteric modulation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion