Elucidating the dynamics of the 3D GPCRome

G Protein-Coupled Receptors (GPCRs) are a diverse protein family integral to a wide range of physiological processes. Although their three-dimensional structures have been extensively characterised through experimental methods, these approaches provide only static snapshots of these inherently flexi...

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Detalles Bibliográficos
Autor: Aranda-García, David
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/693636
Acceso en línea:http://hdl.handle.net/10803/693636
Access Level:acceso abierto
Palabra clave:Receptor Acoblat a Proteïna G (GPCR)
Biologia estructural
Proteïna G
Descobriment de fàrmacs
Dinàmica molecular (MD)
G protein-Coupled receptor (GPCR)
Structural biology
G-proteins
Drug discovery
Molecular Dynamics (MD)
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Descripción
Sumario:G Protein-Coupled Receptors (GPCRs) are a diverse protein family integral to a wide range of physiological processes. Although their three-dimensional structures have been extensively characterised through experimental methods, these approaches provide only static snapshots of these inherently flexible and dynamic proteins. In this thesis, we have generated two extensive datasets of Molecular Dynamics (MD) simulations of GPCRs, including GPCR-transducer protein complexes. Employing these datasets we explored various dynamic features of GPCRs, such as conformational equilibrium, the formation of pockets and tunnels by membrane lipids and the role played by non-covalent interactions in transducer selectivity. Additionally, we have developed interactive online tools within the GPCRmd web server (www.gpcrmd.org) to make our results replicable and accessible to the broader scientific community. These unprecedented datasets and insights shed light on critical aspects of GPCR dynamic functionality, provide new tools for MD simulation analysis and open new avenues for future research in this field.