// Small-molecule med chem — GPCR · Protein pipeline, Phase 6 evidence layer

ADRB2 (β2-adrenergic receptor)

413 aa (P07550) · predicted structure regenerated live for this page (AlphaFold DB + ANM ensemble + fpocket + cross-frame ranker, same pipeline as every worked example on this site).

// Independently verified against a real PDB structure — not pipeline output

Independently checked against PDB 2RH1 (carazolol-bound, the real orthosteric pocket). All 20 of the ligand's real contact residues match, in full — but in the rank-2 cluster, not rank 1. Rank 1 is a different, non-matching cavity. Structural check is the interesting part: whole-chain CA RMSD vs. 2RH1 is a poor 4.63 Å (consistent with no lipid-bilayer context distorting the TM-helix packing), but the pocket region itself is an excellent 0.37 Å — meaning this wasn't a geometry failure, it was purely a ranking failure. The correct answer, and a well-predicted one, is present in the report in full; it's just not the single top pick.

Rank 1 Rank 2 Rank 3

// Sequence

MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
Length413 aa
UniProtP07550
Mean structure confidence0.7914
Pocket clusters3
Numbering cross-walk5/413 vs. 1GQ4

// Confidence flags — rules-based, no learned calibration

cautionNumbering cross-walk against 1GQ4 only mapped 5/413 residues (1%) — the reference structure found is a poor match for most of this sequence (e.g. a short peptide/fragment, or a construct covering only a small domain of a larger protein). Most residues will show as unmapped ('?'); treat any '(literature)' number that DOES appear as coincidental unless independently checked, not as evidence the cross-walk is reliable for this target.

// Findings

Family, precedent, and provenance

Family classification

returned data

7tm_1 (PF00001) — 7 transmembrane receptor (rhodopsin family)

E=4.40e-70 · bit score 236.8 · passes GA threshold: yes

Known ligand precedent

returned data

1561 total structures in family · 24 distinct ligand scaffolds curated

  • 5NM4 — OLA, ZMA, CLR
  • 9H37 — CLR, OLA, A1IR0
  • 9H2X — CLR, A1IR1, OLA
  • 4N6H — OLA, EJ4, TLA
  • 6LPJ — ZMA, CLR, D12, MYS, HEX, 8K6, D10, OCT, UND, ER0, TRD

Conservation

returned data

63 seed sequences · mean pairwise identity 17.8%

Similar known proteins

returned data
  • 7MBX — 17.7% identity · Y01
  • 5WIU — 17.2% identity · AQD, OLA
  • 8CU7 — 17.0% identity · CLR, ETF, LJX, OLA
  • 4EIY — 16.8% identity · CLR, OLA, ZMA
  • 6LPJ — 16.8% identity · 8K6, CLR, D10, D12, ER0, HEX, MYS, OCT, TRD, UND, ZMA

Structure-based (Foldseek)

  • 2Y03 — TM 0.982 · 57% id (new vs. sequence list)
  • 5F8U — TM 0.982 · 58% id (new vs. sequence list)
  • 4AMI — TM 0.980 · 57% id (new vs. sequence list)
  • 8W1V — TM 0.978 · 89% id (new vs. sequence list)
  • 3ZPR — TM 0.977 · 56% id (new vs. sequence list)

Interaction fingerprints (Evidence Integration Layer)

no_ligand_bound_structure

8 ligand-bound structure(s) exist for this target's Pfam family (PF00001), but none checked aligned to the query at >=50% sequence coverage — likely other members of the same broad family (e.g. related kinases), not this specific protein. Interaction fingerprints require a structure of the query protein itself.

Structural analysis — ranked pocket clusters

returned data

Residue numbers below are pipeline-sequential, with the literature (author-deposited PDB 1GQ4) number shown in parentheses — 5/413 residues cross-walked.

RankPersistenceResidues
#1163(?), 64(?), 66(?), 68(?), 69(?), 72(?), 131(?), 134(?), 135(?), 138(?), 226(?), 229(?), 263(?), 264(?), 265(?), 266(?), 267(?), 268(?), 269(?), 270(?) …
#20.890(?), 93(?), 94(?), 97(?), 109(?), 110(?), 113(?), 114(?), 117(?), 118(?), 178(?), 180(?), 191(?), 192(?), 193(?), 194(?), 195(?), 197(?), 199(?), 200(?) …
#3160(?), 61(?), 62(?), 63(?), 337(?), 338(?), 341(?), 343(?), 345(?), 346(?), 347(?), 374(?), 375(?), 376(?), 377(?), 378(?), 379(?)

Pocket functional context (UniProt + ClinVar)

Pocket 1

  • Residue 131: Disulfide bond — Disulfide bond
  • Residue 134: Disulfide bond — Disulfide bond
  • Residue 135: Disulfide bond — Disulfide bond
  • Residue 138: Disulfide bond — Disulfide bond

Pocket 2

  • Residue 109: Disulfide bond — Disulfide bond
  • Residue 110: Disulfide bond — Disulfide bond
  • Residue 113: Binding site — Binding site
  • Residue 113: Binding site — Binding site
  • Residue 113: Binding site — Binding site
  • Residue 113: Disulfide bond — Disulfide bond
  • Residue 114: Disulfide bond — Disulfide bond
  • Residue 117: Disulfide bond — Disulfide bond
  • Residue 118: Binding site — Binding site
  • Residue 118: Disulfide bond — Disulfide bond
  • Residue 178: Disulfide bond — Disulfide bond
  • Residue 180: Disulfide bond — Disulfide bond
  • Residue 191: Disulfide bond — Disulfide bond
  • Residue 203: Binding site — Binding site
  • Residue 293: Binding site — Binding site
  • Residue 293: Binding site — Binding site
  • Residue 312: Binding site — Binding site
  • Residue 312: Binding site — Binding site
  • Residue 312: Binding site — Binding site
  • Residue 316: Binding site — Binding site
  • Residue 316: Binding site — Binding site

Pocket 3

  • Residue 345: Modified residue — Phosphoserine; by PKA
  • Residue 346: Modified residue — Phosphoserine; by PKA

// Limitations & data provenance

Auto-populated from each section’s own status — not hand-maintained.

Family classificationreturned data
Known ligand precedentreturned data
Interaction fingerprintsno_ligand_bound_structure
Functional contextreturned data
Conservationreturned data
Structural analysisreturned data
Similar known proteinsreturned data
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