GPCR receptor pharmacology — agonist/antagonist/inverse-agonist/biased-agonist classification, GPCRdb structural data, receptor-ligand binding analysis, antibody-target interface (SAbDab). Use for GPCR drug discovery, biased-agonism analysis, receptor subtype selectivity questions, and orthosteric vs allosteric pocket characterization.
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GPCR and Structural Pharmacology Research
GPCR pharmacology: agonist vs antagonist vs inverse agonist vs biased agonist — each has different clinical implications. Biased agonism (preferential G-protein vs β-arrestin signaling) can separate efficacy from side effects; for example, G-protein-biased opioid agonists aim to retain analgesia while reducing β-arrestin-mediated respiratory depression. Always classify retrieved ligands by their pharmacological type, not just their chemical structure. Receptor state (active vs inactive crystal structure) determines which ligands and mutations are interpretable — an inactive-state structure is appropriate for antagonist binding analysis, active-state for agonist-bound complexes. Generic GPCR numbering (Ballesteros-Weinstein) enables cross-receptor mutation comparison; always report positions in this system alongside sequence positions.
LOOK UP DON'T GUESS: never assume GPCRdb entry names (e.g., adrb2_human) or PDB IDs — always use GPCRdb_list_proteins to find the correct entry name and GPCRdb_get_structures to confirm available structures.
Research skill integrating GPCRdb (GPCR receptor biology), SAbDab (antibody structures), and PDBePISA (protein interface analysis) to support structural pharmacology, antibody engineering, and GPCR-targeted drug discovery.
KEY PRINCIPLES:
Receptor-first — Identify GPCR entry name before any GPCRdb queries
Structure-guided — Pair GPCRdb mutation data with PDB structures via PDBePISA
Antibody context — Use SAbDab for therapeutic antibody structure retrieval and CDR analysis
English-first queries — Use standard receptor names (e.g., "beta-2 adrenergic receptor") in searches; convert to GPCRdb entry names for API calls
When to Use
Apply when user asks:
"What ligands are known for [GPCR receptor]?"
"What crystal structures exist for [receptor]?"
"Find antibody structures targeting [antigen]"
"Analyze the protein-protein interface in PDB [ID]"
"What mutations affect [GPCR] function or pharmacology?"
"Which GPCRs are in the [family] family?"
"What are the CDR loops in antibody PDB [ID]?"
"What is the biological assembly for [PDB ID]?"
Tool Parameter Reference (CRITICAL)
Tool
Key Parameters
Notes
GPCRdb_get_protein
protein
GPCRdb entry name (e.g., adrb2_human), NOT gene symbol or UniProt accession
GPCRdb_list_proteins
family (optional), protein_class (optional)
Lists all GPCRs; filter by family slug (e.g., "adrenoceptors") OR by human-readable class name via protein_class (e.g., "chemokine receptors", "opioid receptors")
GPCRdb_get_structures
protein (optional), state (optional)
state: "active", "inactive", "intermediate"
GPCRdb_get_ligands
protein
Returns agonists, antagonists, biased ligands with affinities
GPCRdb_get_mutations
protein
Returns mutation effects on receptor function and ligand binding
SAbDab_search_structures
query
Antigen name, species, or keywords; returns browse URL + metadata
4-character PDB code; returns all interface pairs with buried area
PDBePISA_get_assemblies
pdb_id
Predicted biological assemblies from crystal packing
PDBePISA_get_monomer_analysis
pdb_id
Per-chain solvent-accessible surface area (SASA) breakdown
GPCRdb Entry Name Format
GPCRdb uses its own entry name format: {receptor_slug}_{species}. Common examples:
Beta-2 adrenergic receptor: adrb2_human
Beta-1 adrenergic receptor: adrb1_human
Mu-opioid receptor: oprm1_human
Dopamine D2 receptor: drd2_human
Glucagon-like peptide-1 receptor: glp1r_human
CXCR4 chemokine receptor: cxcr4_human
If entry name is unknown, use GPCRdb_list_proteins() to browse and find the correct slug. You can also filter by receptor class using the protein_class parameter with a human-readable name — e.g., GPCRdb_list_proteins(protein_class="chemokine receptors") — instead of the numeric family slug. Both family and protein_class are accepted and serve overlapping purposes; prefer protein_class when the user provides a receptor class name.
Workflow Overview
Phase 1: Receptor Identification (for GPCR queries)
-> GPCRdb_list_proteins: find receptor family and entry name
-> GPCRdb_get_protein: receptor details, family, species
Phase 2: Ligand Landscape
-> GPCRdb_get_ligands: all known ligands by pharmacology class
-> Cross-reference with ChEMBL/PubChem for chemical properties
Phase 3: Structural Data
-> GPCRdb_get_structures: available PDB/EMDB structures with resolution
-> PDBePISA_get_interfaces: interface analysis on best structure
-> PDBePISA_get_assemblies: biological assembly determination
Phase 4: Mutation & Pharmacology Data
-> GPCRdb_get_mutations: pharmacological mutation map
-> Compare to ligand binding sites from structure
Phase 5: Antibody Structures (for antibody queries)
-> SAbDab_search_structures: find structures by antigen
-> SAbDab_get_structure: CDR annotations, chain details
-> PDBePISA_get_interfaces: antibody-antigen interface analysis
Phase 1: GPCR Receptor Identification
# List all GPCRs in a family to find entry name (by slug)
family_list = GPCRdb_list_proteins(family="adrenoceptors")
# Filter by human-readable class name (new -- preferred when user says e.g. "chemokine receptors")
chemokine_list = GPCRdb_list_proteins(protein_class="chemokine receptors")
# Browse all GPCRs (no family filter)
all_gpcrs = GPCRdb_list_proteins()
# Get detailed protein info once you have the entry name
receptor = GPCRdb_get_protein(protein="adrb2_human")
# Returns: family classification, endogenous ligands, tissue expression,# GPCRdb-specific annotations, sequence features
Phase 2: Ligand Landscape
# Get all known ligands for a GPCR
ligands = GPCRdb_get_ligands(protein="adrb2_human")
# Returns: ligand names, types (agonist/antagonist/partial/biased/allosteric),# binding affinities (Ki, IC50, EC50), references# Ligand type classification:# - Agonist: activates receptor# - Antagonist/Inverse agonist: blocks or suppresses receptor# - Partial agonist: submaximal activation# - Biased agonist: selective signaling (Gs vs. beta-arrestin bias)# - Positive/Negative allosteric modulator (PAM/NAM)
After retrieving ligands from GPCRdb, optionally cross-reference with:
PubChem_get_CID_by_compound_name(compound_name=ligand_name) — get CID, SMILES
ChEMBL_search_molecules(query=ligand_name) — get ChEMBL ID, bioactivity data
Phase 3: Structural Data
# Get available crystal/cryo-EM structures
structures = GPCRdb_get_structures(protein="adrb2_human", state="inactive")
# state options: "active", "inactive", "intermediate" (omit for all)# Returns: PDB IDs, resolution, ligand in structure, publication info# Analyze a specific structure's interfaces
interfaces = PDBePISA_get_interfaces(pdb_id="2rh1") # adrb2 inactive structure# Returns: interface pairs, buried solvent-accessible area (BSA),# interface residues, hydrogen bonds, salt bridges# Determine biological assembly
assemblies = PDBePISA_get_assemblies(pdb_id="2rh1")
# Returns: predicted oligomeric state, assembly stability score,# subunit composition# Per-chain SASA breakdown
monomers = PDBePISA_get_monomer_analysis(pdb_id="2rh1")
# Returns: accessible/buried surface area per chain
