// Fragment-based drug discovery — kinase · Protein pipeline, Phase 6 evidence layer

CDK2

298 aa (P24941) · 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 1HCK (ATP-bound). The rank-1 cluster (persistence 1.0) exactly matches all 22 of 22 real ATP-site contact residues — 100% — including the hinge residues and the catalytic lysine. Structural check: whole-chain CA RMSD vs. 1HCK is 1.87 Å; excluding the flexible activation loop (residues ~153-162, known to be disordered in CDK2 without cyclin binding) and chain termini, the core domain matches at 0.82 Å.

Rank 1 Rank 2 Rank 3

// Sequence

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Length298 aa
UniProtP24941
Mean structure confidence0.8846
Pocket clusters3
Numbering cross-walk281/298 vs. 6Q4G

// Findings

Family, precedent, and provenance

Family classification

returned data

Pkinase (PF00069) — Protein kinase domain

E=1.90e-77 · bit score 260.9 · passes GA threshold: yes

Known ligand precedent

returned data

4850 total structures in family · 9 distinct ligand scaffolds curated

  • 6TGU — N92
  • 9Q9D — 3NG, R9G
  • 9Q8C — T9Y
  • 9Q9G — R9J
  • 9QAB — RA7, 3NG

Conservation

returned data

37 seed sequences · mean pairwise identity 23.4%

Similar known proteins

returned data
  • 6Q49 — 95.9% identity · HGQ
  • 6Q4H — 95.9% identity · HGH
  • 6Q48 — 95.9% identity · HHQ
  • 6Q4J — 95.9% identity · HHB
  • 6Q4E — 95.9% identity · HH5

Structure-based (Foldseek)

  • 2VTQ — TM 0.989 · 92% id (new vs. sequence list)
  • 5AND — TM 0.989 · 93% id (new vs. sequence list)
  • 4FKS — TM 0.989 · 93% id (new vs. sequence list)
  • 4FKJ — TM 0.988 · 93% id (new vs. sequence list)
  • 2W05 — TM 0.988 · 93% id (new vs. sequence list)

Interaction fingerprints (Evidence Integration Layer)

returned data

Representative complex: 6Q49 (HGQ, 1.00 Å)

Residue (PDB)Residue (pipeline)InteractionPartner
268268hydrogen bondHIS268 (hydrogen bond) with ligand HGQ
269269hydrogen bondTYR269 (hydrogen bond) with ligand HGQ
245245pi cationARG245 (pi cation) with ligand HGQ
226226hydrophobicVAL226 (hydrophobic) with ligand HGQ
270270water bridgeASP270 (water bridge) with ligand HGQ
245245water bridgeARG245 (water bridge) with ligand HGQ
264264water bridgeSER264 (water bridge) with ligand HGQ
264264water bridgeSER264 (water bridge) with ligand HGQ

Representative complex: 6Q4H (HGH, 1.00 Å)

Residue (PDB)Residue (pipeline)InteractionPartner
8383hydrogen bondLEU83 (hydrogen bond) with ligand HGH
3333hydrogen bondLYS33 (hydrogen bond) with ligand HGH
1414hydrogen bondTHR14 (hydrogen bond) with ligand HGH
1414hydrogen bondTHR14 (hydrogen bond) with ligand HGH
145145hydrogen bondASP145 (hydrogen bond) with ligand HGH
8383hydrogen bondLEU83 (hydrogen bond) with ligand HGH
129129salt bridgeLYS129 (salt bridge) with ligand HGH
1818hydrophobicVAL18 (hydrophobic) with ligand HGH
1818hydrophobicVAL18 (hydrophobic) with ligand HGH
131131hydrophobicGLN131 (hydrophobic) with ligand HGH
1010hydrophobicILE10 (hydrophobic) with ligand HGH
132132water bridgeASN132 (water bridge) with ligand HGH
132132water bridgeASN132 (water bridge) with ligand HGH

Representative complex: 6Q48 (HHQ, 1.03 Å)

Residue (PDB)Residue (pipeline)InteractionPartner
8383hydrogen bondLEU83 (hydrogen bond) with ligand HHQ

Structural analysis — ranked pocket clusters

returned data

Residue numbers below are pipeline-sequential, with the literature (author-deposited PDB 6Q4G) number shown in parentheses — 281/298 residues cross-walked.

RankPersistenceResidues
#118(8), 9(9), 10(10), 11(11), 12(12), 13(13), 14(14), 15(15), 16(16), 18(18), 20(20), 31(31), 33(33), 64(64), 80(80), 81(81), 82(82), 83(83), 84(84), 85(85) …
#2114(14), 15(15), 126(126), 127(127), 128(128), 129(129), 131(131), 149(149), 154(?), 155(?), 156(?), 158(?), 160(?), 162(?), 163(?), 164(164), 165(165), 168(168), 169(169), 170(170) …
#3151(51), 54(54), 55(55), 57(57), 58(58), 121(121), 122(122), 123(123), 124(124), 125(125), 126(126), 147(147), 149(149), 150(150), 151(151)

Pocket residues overlapping known interaction sites

  • Pocket 1: residues 10, 14, 18, 33, 83, 129, 131, 132, 145 (9 of 34 pocket residues match a known interaction site)
  • Pocket 2: residues 14, 129, 131 (3 of 23 pocket residues match a known interaction site)
  • Pocket 3: no overlap with known interaction sites (15 checked)

Pocket functional context (UniProt + ClinVar)

Pocket 1

  • Residue 9: Site — CDK7 binding
  • Residue 10: Binding site — Binding site
  • Residue 11: Binding site — Binding site
  • Residue 12: Binding site — Binding site
  • Residue 13: Binding site — Binding site
  • Residue 14: Binding site — Binding site
  • Residue 14: Binding site — Binding site
  • Residue 14: Modified residue — Phosphothreonine
  • Residue 15: Binding site — Binding site
  • Residue 15: Modified residue — Phosphotyrosine; by WEE1
  • Residue 16: Binding site — Binding site
  • Residue 18: Binding site — Binding site
  • Residue 33: Binding site — Binding site
  • Residue 33: Binding site — Binding site
  • Residue 81: Binding site — Binding site
  • Residue 81: Binding site — Binding site
  • Residue 82: Binding site — Binding site
  • Residue 83: Binding site — Binding site
  • Residue 83: Binding site — Binding site
  • Residue 86: Binding site — Binding site
  • Residue 89: Site — CDK7 binding
  • Residue 127: Active site — Proton acceptor
  • Residue 127: Binding site — Binding site
  • Residue 129: Binding site — Binding site
  • Residue 131: Binding site — Binding site
  • Residue 132: Binding site — Binding site
  • Residue 132: Binding site — Binding site
  • Residue 145: Binding site — Binding site
  • Residue 145: Binding site — Binding site

Pocket 2

  • Residue 14: Binding site — Binding site
  • Residue 14: Binding site — Binding site
  • Residue 14: Modified residue — Phosphothreonine
  • Residue 15: Binding site — Binding site
  • Residue 15: Modified residue — Phosphotyrosine; by WEE1
  • Residue 127: Active site — Proton acceptor
  • Residue 127: Binding site — Binding site
  • Residue 129: Binding site — Binding site
  • Residue 131: Binding site — Binding site
  • Residue 160: Modified residue — Phosphothreonine; by CAK and CCRK

Pocket 3

no UniProt functional features or ClinVar variants overlap with pocket residues

// Limitations & data provenance

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

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