GPCRDB

GPCRDB provides curated sequences, structures, receptor mutations, ligands, pharmacological profiles and analytical tools for the study of G protein‑coupled receptors (GPCRs) and their structure–function relationships.

Key Features:

• Reference Data: Curated datasets include sequences, structures, receptor point mutations, ligands and pharmacological profiles integrated from ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem with ligand bioactivity, vendor details and physicochemical descriptors.
• Interactive Visualization: Visualization tools include snakeplots, helix box plots and phylogenetic trees with color‑coded receptor classifications for residue and evolutionary analyses.
• Structural Analysis Tools: Structural capabilities comprise browsing GPCR crystal structures, structure superposition, ligand interaction inspection, structure similarity assessments, secondary structure evaluations, protein backbone packing analyses, residue‑residue contact networks and amino‑acid property correlations to inform mutagenesis.
• Experiment Design: Resources support sequence alignments, comparative structure analysis to identify functional determinants, trees clustering GPCR structures by 3D conformation, and state‑specific structure models of all human non‑olfactory GPCRs built using AlphaFold2‑MultiState.
• Data Deposition: Facility to deposit point mutations and their effects on ligand binding for incorporation into the curated datasets.

Scientific Applications:

• Drug design studies: Use receptor structures, ligand bioactivity and pharmacological profiles to investigate receptor structure–function relationships relevant to ligand discovery and optimization.
• Context‑specific signaling analysis: Explore tissue‑specific GPCR signaling and the roles of isoform diversity and combinatorial expression in receptor signaling and drug responses.
• Mutagenesis and functional mapping: Design and interpret mutagenesis experiments using residue contact networks, structural comparisons and state‑specific models to identify functional determinants.

Methodology:

Data curation and integration from ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem; sequence alignments; structure superposition; structure similarity and secondary‑structure evaluations; protein backbone packing analyses; residue‑residue contact network and amino‑acid property correlation calculations; clustering of GPCR structures by 3D conformation; and generation of state‑specific models using AlphaFold2‑MultiState.