Integrative biophysical illumination of the 3D GPCRome dynamics
Insights into the dynamics of G-protein-coupled receptors (GPCRs) remain limited. Here we present an integrative strategy that bridges computational and experimental biophysical methods for probing protein dynamics. To illustrate its potential, we developed GPCRmd-NMR, a platform that synergistically combines molecular dynamics (MD) simulations with high-resolution nuclear magnetic resonance (NMR) spectroscopy across the three-dimensional GPCRome. The resulting dataset enables structure-resolved analysis by applying the strategy across multiple GPCRs. We provide access to underexplored functional GPCR dynamics, receptor states and sites, including microswitches, hidden ligand entrance gateways and intrinsically disordered regions. Our integrated framework offers a solution to challenges faced by both experimental and computational researchers including the MD-NMR timescale gap.
Authors
- David Aranda-García (ORCID: https://orcid.org/0000-0002-5476-2903)
- Franz Hagn (ORCID: https://orcid.org/0000-0002-1315-459X)
- Mariona Torrens‐Fontanals (ORCID: https://orcid.org/0000-0001-6233-8945)
- Jiafei Mao (ORCID: https://orcid.org/0000-0003-1547-325X)
- Aditya Prasad Patra
- Brian Medel-Lacruz (ORCID: https://orcid.org/0000-0003-2831-7731)
- Massimiliano Bonomi (ORCID: https://orcid.org/0000-0002-7321-0004)
- Tomasz Maciej Stępniewski (ORCID: https://orcid.org/0000-0002-6828-9192)
- Jana Selent (ORCID: https://orcid.org/0000-0002-1844-4449)
- Adrián García‐Recio (ORCID: https://orcid.org/0000-0002-7143-9075)
Institutions
- Goethe University Frankfurt (DE)
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- Universitat Pompeu Fabra (ES)
- Université Paris Cité (FR)
- Helmholtz Zentrum München (DE)
- Beijing National Laboratory for Molecular Sciences (CN)
- Max Planck Institute of Biophysics (DE)
- Hospital Del Mar (ES)
- Municipal Institute for Medical Research (ES)
- Hospital del Mar Research Institute (ES)
- Biologie Moléculaire Structurale et Processus Infectieux (FR)
- Parc Científic de Barcelona (ES)
- Technical University of Munich (DE)
Publication Details
- Journal
- Nature Structural & Molecular Biology
- Published
- 2026-10-27
- DOI
- https://doi.org/10.1038/s41594-026-01891-8
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Generalitat de Catalunya
- Goethe-Universität Frankfurt am Main
- HORIZON EUROPE Framework Programme
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación
- Beijing National Laboratory for Molecular Sciences
- NextGenerationEU