GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources

Area of Science:

• Pharmacology
• Biochemistry
• Structural Biology

Background:

• G protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
• GPCRdb serves as a vital resource for over 5000 researchers monthly, providing essential data and tools for GPCR studies.

Purpose of the Study:

• To present the fifth major release of the GPCRdb, introducing significant updates and new functionalities.
• To enhance resources for receptor sequences, structures, ligands, and analysis tools for GPCR research.

Main Methods:

• Incorporation of class D generic residue numbers and a comparative structure analysis tool.
• Generation of state-specific structure models for human non-olfactory GPCRs using AlphaFold2-MultiState.
• Integration of comprehensive endogenous and surrogate ligand data from multiple databases (ChEMBL, Guide to Pharmacology, PDSP Ki, PubChem).

Main Results:

• New additions include class D residue numbers, a comparative structure analysis tool, and 3D conformation-based structure clustering.
• State-specific structure models for all human non-olfactory GPCRs are now available.
• An expanded ligand resource integrates data on bioactivity, vendors, and physicochemical properties.

Conclusions:

• The updated GPCRdb provides a comprehensive, one-stop-shop resource for interdisciplinary GPCR research.
• Enhanced data and tools facilitate deeper understanding and design of experiments related to GPCRs and their ligands.