// Oncology · Protein pipeline, Phase 6 evidence layer

KRAS

189 aa (P01116) · 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 6OIM (KRAS G12C + sotorasib/AMG-510 — the drug that made this GTPase druggable). The rank-1 cluster (persistence 1.0, all 5 ensemble frames) exactly matches 6 of the ligand's 21 real contact residues — 13, 16, 34, 58, 60, 61, spanning the P-loop, switch I, and the switch-II cryptic pocket — found unprompted. Structural check: whole-chain CA RMSD vs. 6OIM is 1.69 Å; the pocket region itself is 1.96 Å (some deviation expected — 6OIM is a specific GDP/inhibitor-bound conformational state, and KRAS's switch regions are known to be flexible across nucleotide states).

Rank 1 Rank 2 Rank 3

// Sequence

MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGCVKIKKCIIM
Length189 aa
UniProtP01116
Mean structure confidence0.9152
Pocket clusters3
Numbering cross-walk161/189 vs. 9IAY

// Findings

Family, precedent, and provenance

Family classification

returned data

Ras (PF00071) — Ras family

E=6.80e-61 · bit score 205.3 · passes GA threshold: yes

Known ligand precedent

returned data

1566 total structures in family · 10 distinct ligand scaffolds curated

  • 9IAY — GDP, WYU
  • 9IAW — GDP, A1I1R
  • 2CE2 — XY2, GDP
  • 3X1X — CD, GNP
  • 8ONV — VU6, GDP

Conservation

returned data

60 seed sequences · mean pairwise identity 39.3%

Similar known proteins

returned data
  • 8EDY — 86.8% identity · GDP
  • 8EER — 86.8% identity · GDP
  • 9G4B — 82.3% identity · A1IIU, GDP
  • 9GGV — 82.3% identity · A1IK9, GDP
  • 8TVK — 81.0% identity · GDP

Structure-based (Foldseek)

  • 6V6F — TM 1.000 · 96% id (new vs. sequence list)
  • 6ZIZ — TM 1.000 · 92% id (new vs. sequence list)
  • 2UZI — TM 1.000 · 94% id (new vs. sequence list)
  • 8ELU — TM 1.000 · 94% id (new vs. sequence list)
  • 8EM0 — TM 1.000 · 94% id (new vs. sequence list)

Interaction fingerprints (Evidence Integration Layer)

returned data

Representative complex: 9IAY (GDP, 0.95 Å)

Residue (PDB)Residue (pipeline)InteractionPartner
1111hydrogen bondALA11 (hydrogen bond) with ligand GDP
3030hydrogen bondASP30 (hydrogen bond) with ligand GDP
3030hydrogen bondASP30 (hydrogen bond) with ligand GDP
3232hydrogen bondTYR32 (hydrogen bond) with ligand GDP
1313hydrogen bondGLY13 (hydrogen bond) with ligand GDP
1616hydrogen bondLYS16 (hydrogen bond) with ligand GDP
1717hydrogen bondSER17 (hydrogen bond) with ligand GDP
1414hydrogen bondVAL14 (hydrogen bond) with ligand GDP
1515hydrogen bondGLY15 (hydrogen bond) with ligand GDP
1818hydrogen bondALA18 (hydrogen bond) with ligand GDP
117117hydrogen bondLYS117 (hydrogen bond) with ligand GDP
116116hydrogen bondASN116 (hydrogen bond) with ligand GDP
117117hydrogen bondLYS117 (hydrogen bond) with ligand GDP
146146hydrogen bondALA146 (hydrogen bond) with ligand GDP
147147hydrogen bondLYS147 (hydrogen bond) with ligand GDP
2828pi stackingPHE28 (pi stacking) with ligand GDP
2828pi stackingPHE28 (pi stacking) with ligand GDP
1616salt bridgeLYS16 (salt bridge) with ligand GDP
119119salt bridgeASP119 (salt bridge) with ligand GDP
3434water bridgePRO34 (water bridge) with ligand GDP
3434water bridgePRO34 (water bridge) with ligand GDP
3232water bridgeTYR32 (water bridge) with ligand GDP
6060water bridgeGLY60 (water bridge) with ligand GDP

Representative complex: 2CE2 (XY2, 1.00 Å)

Residue (PDB)Residue (pipeline)InteractionPartner
3333hydrogen bondASP33 (hydrogen bond) with ligand XY2
2525hydrogen bondGLN25 (hydrogen bond) with ligand XY2
4040pi stackingTYR40 (pi stacking) with ligand XY2
4040pi stackingTYR40 (pi stacking) with ligand XY2
5757water bridgeASP57 (water bridge) with ligand XY2

Representative complex: 3X1X (CD, 1.00 Å)

no interactions detected in reference structure 3X1X for ligand CD — check structure selection

2/3 representative structure(s) produced interaction data

Structural analysis — ranked pocket clusters

returned data

Residue numbers below are pipeline-sequential, with the literature (author-deposited PDB 9IAY) number shown in parentheses — 161/189 residues cross-walked.

RankPersistenceResidues
#1113(13), 15(15), 16(16), 17(17), 18(18), 21(21), 28(28), 29(29), 30(30), 31(31), 32(32), 33(33), 34(34), 35(35), 36(36), 37(37), 38(38), 40(40), 58(58), 60(60) …
#2197(97), 107(107), 108(108), 109(109), 110(110), 111(111), 137(137), 138(138), 139(139), 162(162), 165(?), 166(?), 169(?)
#3173(73), 74(74), 75(75), 76(76), 104(104), 106(106), 109(109), 110(110), 163(163), 166(?), 167(?), 170(?)

Pocket residues overlapping known interaction sites

  • Pocket 1: residues 13, 15, 16, 17, 18, 28, 30, 32, 33, 34, 40, 60, 116, 117, 119, 146, 147 (17 of 27 pocket residues match a known interaction site)
  • Pocket 2: no overlap with known interaction sites (13 checked)
  • Pocket 3: no overlap with known interaction sites (12 checked)

Pocket functional context (UniProt + ClinVar)

Pocket 1

  • Residue 13: Binding site — Binding site
  • Residue 13: ClinVar variant [Pathogenic] — G13R (NM_004985.5(KRAS):c.36_37delinsGC (p.Gly13Arg))
  • Residue 15: Binding site — Binding site
  • Residue 16: Binding site — Binding site
  • Residue 17: Binding site — Binding site
  • Residue 17: Binding site — Binding site
  • Residue 18: Binding site — Binding site
  • Residue 18: ClinVar variant [Pathogenic] — A18V (NM_004985.5(KRAS):c.53C>T (p.Ala18Val))
  • Residue 28: Binding site — Binding site
  • Residue 29: Binding site — Binding site
  • Residue 30: Binding site — Binding site
  • Residue 34: ClinVar variant [Likely pathogenic] — P34Q (NM_004985.5(KRAS):c.101C>A (p.Pro34Gln))
  • Residue 35: Glycosylation — (Microbial infection) O-linked (Glc) threonine; by P.sordellii toxin TcsL
  • Residue 61: ClinVar variant [Pathogenic] — Q61R (NM_004985.5(KRAS):c.182_183delinsGT (p.Gln61Arg))
  • Residue 116: Binding site — Binding site
  • Residue 117: Binding site — Binding site
  • Residue 117: ClinVar variant [Likely pathogenic] — K117R (NM_004985.5(KRAS):c.350A>G (p.Lys117Arg))
  • Residue 117: ClinVar variant [Likely pathogenic] — K117T (NM_004985.5(KRAS):c.350A>C (p.Lys117Thr))
  • Residue 119: Binding site — Binding site
  • Residue 146: Binding site — Binding site
  • Residue 147: Binding site — Binding site
  • Residue 147: ClinVar variant [Likely pathogenic] — K147N (NM_004985.5(KRAS):c.441G>T (p.Lys147Asn))
  • Residue 147: ClinVar variant [Likely pathogenic] — K147M (NM_004985.5(KRAS):c.440A>T (p.Lys147Met))

Pocket 2

  • Residue 166: Region — Hypervariable region
  • Residue 169: Region — Hypervariable region

Pocket 3

  • Residue 104: Modified residue — N6-acetyllysine
  • Residue 166: Region — Hypervariable region
  • Residue 167: Region — Hypervariable region
  • Residue 170: Region — Hypervariable region

// 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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