GPCRdb in 2018: adding GPCR structure models and ligands

By Gáspár Pándy-Szekeres, Christian Munk, Ts. Tsonkov, Stefan Mordalski, Kasper Harpsøe, Alexander Sebastian Hauser, Andrzej J. Bojarski, David E. Gloriam. 2017

500 citations recorded by the source corpus.

Abstract G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of ‘Less model – more Xtal’, each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions. Models are provided for inactive, intermediate and active states—except for classes C and F that so far only have inactive templates. The ligand database has separate browsers for: (i) target selection by receptor, family or class, (ii) ligand filtering based on cross-experiment activities (min, max and mean) or chemical properties, (iii) ligand source data and (iv) commercial availability. SMILES structures and activity spreadsheets can be downloaded for further processing. Furthermore, three recent landmark publications on GPCR drugs, G protein selectivity and genetic variants have been accompanied with resources that now let readers view and analyse the findings themselves in GPCRdb. Altogether, this update will enable scientific investigation for the wider GPCR community. GPCRdb is available at http://www.gpcrdb.org.

Subfields: Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Molecular Biology

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Citations in the corpus

Multi-State Modeling of G-protein Coupled Receptors at Experimental Accuracy (2021, neutral): “However, the accuracy of these GPCR models has not been rigorously benchmarked, especially with respect to reproducing differences between active and inactive states and in light of the recent advances in structure prediction accuracy.(25) Baek et al.”
GPCRdb in 2021: integrating GPCR sequence, structure and function (2020, methodology): “GPCRdb enriches the ligand data by integrating physicochemical properties and their commercial availability (23).”
GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models (2018, background): “Currently, there are over 200 structures of GPCRs in the Protein Data Bank (PDB) with about 50 unique receptor types (1).”
Pharmacogenomics of GPCR Drug Targets (2018, unknown): “Each variant was mapped to its respective structural segment (e.g., transmembrane regions, intra-cellular loops, extra-cellular loops, etc.), generic residue position (i.e., GPCRdb numbering), receptor class, ligand-type and family classiﬁcation according to the GuideToPharmacology (Southan et al., ”
An Online Resource for GPCR Structure Determination and Analysis (2019, unknown): “2) 20,21 .”
AlphaFold2 versus experimental structures: evaluation on G protein-coupled receptors (2022, methodology): “org/structure/) according to the open degree of the TM6 helix [39, 40].”
GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources (2022, methodology): “The use of AlphaFoldMultiState removed the need for alternative backbone templates in our previously published GPCRdb’s structure modelling pipeline (18,19).”
Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors (2019, methodology): “More specifically, consensus peptide receptor family sequences were compared to non-peptide receptor families for every generic position based on the GPCRdb numbering scheme.”