// Small-molecule med chem · Protein pipeline, Phase 6 evidence layer
MDM2
491 aa (Q00987) · 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 1YCR (MDM2 + p53 transactivation peptide, the structure that defined the nutlin-class inhibitor pocket). The rank-1 cluster (persistence 1.0) exactly matches 8 of 22 real p53-contact residues — 25, 26, 50, 51, 94, 96, 100, 104 — landing precisely on the real, druggable PPI cleft. Structural check: CA RMSD vs. 1YCR is 0.49 Å whole-domain, 0.61 Å within the pocket residues specifically — near-experimental accuracy on the resolved N-terminal domain.
// Sequence
// Confidence flags — rules-based, no learned calibration
// Findings
Family, precedent, and provenance
Family classification
returned datazf-C3HC4_3 (PF13920) — Zinc finger, C3HC4 type (RING finger)
E=1.10e-10 · bit score 41.9 · passes GA threshold: yes
Known ligand precedent
returned data74 total structures in family · 8 distinct ligand scaffolds curated
- 13SY — W2J
- 13SQ — U0P
- 13SL — JHP
- 13ST — A1H9V
- 13SW — A1AJM
Conservation
returned data309 seed sequences · mean pairwise identity 29.4%
Similar known proteins
returned data- 3T6P — 4.4% identity · (none)
- 9SA1 — 0.0% identity · (none)
- 9SA2 — 0.0% identity · (none)
- 6SQP — 0.0% identity · (none)
- 13SY — 0.0% identity · W2J
Structure-based (Foldseek)
- 4HFZ — TM 1.000 · 98% id (new vs. sequence list)
- 3LNZ — TM 1.000 · 100% id (new vs. sequence list)
- 3TPX — TM 1.000 · 100% id (new vs. sequence list)
- 5UMM — TM 1.000 · 100% id (new vs. sequence list)
- 3IWY — TM 1.000 · 100% id (new vs. sequence list)
Interaction fingerprints (Evidence Integration Layer)
no_ligand_bound_structure8 ligand-bound structure(s) exist for this target's Pfam family (PF13920), 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 dataResidue numbers below are pipeline-sequential, with the literature (author-deposited PDB 6Q9L) number shown in parentheses — 94/491 residues cross-walked.
| Rank | Persistence | Residues |
|---|---|---|
| #1 | 1 | 23(23), 24(24), 25(25), 26(26), 49(49), 50(50), 51(51), 94(94), 95(95), 96(96), 97(97), 98(98), 100(100), 101(101), 104(104), 190(?), 191(?), 192(?), 193(?), 194(?) … |
| #2 | 1 | 263(?), 266(?), 268(?), 270(?), 271(?), 272(?), 273(?), 274(?), 275(?), 276(?), 462(?), 463(?), 466(?), 467(?), 469(?), 470(?), 484(?), 485(?), 486(?), 487(?) … |
| #3 | 1 | 275(?), 276(?), 277(?), 278(?), 279(?), 280(?), 282(?), 428(?), 429(?), 430(?), 431(?), 449(?), 458(?), 486(?), 487(?), 488(?), 489(?), 490(?), 491(?) |
Pocket functional context (UniProt + ClinVar)
Pocket 1
- Residue 23: Region — Necessary for interaction with USP2
- Residue 23: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 24: Region — Necessary for interaction with USP2
- Residue 24: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 25: Region — Necessary for interaction with USP2
- Residue 25: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 26: Region — Necessary for interaction with USP2
- Residue 26: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 49: Region — Necessary for interaction with USP2
- Residue 49: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 50: Region — Necessary for interaction with USP2
- Residue 50: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 51: Region — Necessary for interaction with USP2
- Residue 51: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 94: Region — Necessary for interaction with USP2
- Residue 94: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 95: Region — Necessary for interaction with USP2
- Residue 95: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 96: Region — Necessary for interaction with USP2
- Residue 96: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 97: Region — Necessary for interaction with USP2
- Residue 97: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 98: Region — Necessary for interaction with USP2
- Residue 98: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 100: Region — Necessary for interaction with USP2
- Residue 100: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 101: Region — Necessary for interaction with USP2
- Residue 101: Region — Sufficient to promote the mitochondrial pathway of apoptosis
- Residue 104: Region — Necessary for interaction with USP2
- Residue 190: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 190: Region — Interaction with MTBP
- Residue 190: Modified residue — Phosphoserine
- Residue 191: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 191: Region — Interaction with MTBP
- Residue 192: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 192: Region — Interaction with MTBP
- Residue 193: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 193: Region — Interaction with MTBP
- Residue 194: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 194: Region — Interaction with MTBP
- Residue 195: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 195: Region — Interaction with MTBP
- Residue 196: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 196: Region — Interaction with MTBP
- Residue 197: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 197: Region — Interaction with MTBP
- Residue 198: Region — Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
- Residue 198: Region — Interaction with MTBP
Pocket 2
- Residue 263: Region — Interaction with MTBP
- Residue 263: Region — Mediates interaction with RAD54B
- Residue 263: Region — ARF-binding
- Residue 263: Region — Region II
- Residue 263: Region — Disordered
- Residue 266: Region — Interaction with MTBP
- Residue 266: Region — Mediates interaction with RAD54B
- Residue 266: Region — ARF-binding
- Residue 266: Region — Region II
- Residue 266: Region — Disordered
- Residue 268: Region — Interaction with MTBP
- Residue 268: Region — Mediates interaction with RAD54B
- Residue 268: Region — ARF-binding
- Residue 268: Region — Region II
- Residue 268: Region — Disordered
- Residue 270: Region — Interaction with MTBP
- Residue 270: Region — Mediates interaction with RAD54B
- Residue 270: Region — ARF-binding
- Residue 270: Region — Region II
- Residue 270: Region — Disordered
- Residue 271: Region — Interaction with MTBP
- Residue 271: Region — Mediates interaction with RAD54B
- Residue 271: Region — ARF-binding
- Residue 271: Region — Region II
- Residue 271: Region — Disordered
- Residue 272: Region — Interaction with MTBP
- Residue 272: Region — Mediates interaction with RAD54B
- Residue 272: Region — ARF-binding
- Residue 272: Region — Region II
- Residue 272: Region — Disordered
- Residue 273: Region — Interaction with MTBP
- Residue 273: Region — Mediates interaction with RAD54B
- Residue 273: Region — ARF-binding
- Residue 273: Region — Region II
- Residue 273: Region — Disordered
- Residue 274: Region — Interaction with MTBP
- Residue 274: Region — Mediates interaction with RAD54B
- Residue 274: Region — ARF-binding
- Residue 274: Region — Region II
- Residue 274: Region — Disordered
- Residue 275: Region — Interaction with MTBP
- Residue 275: Region — Mediates interaction with RAD54B
- Residue 275: Region — ARF-binding
- Residue 275: Region — Region II
- Residue 276: Region — Interaction with MTBP
- Residue 276: Region — Mediates interaction with RAD54B
- Residue 276: Region — ARF-binding
- Residue 276: Region — Region II
- Residue 276: Region — Necessary for interaction with USP2
- Residue 462: Region — Necessary for interaction with USP2
- Residue 463: Region — Necessary for interaction with USP2
- Residue 466: Region — Necessary for interaction with USP2
- Residue 467: Region — Necessary for interaction with USP2
- Residue 469: Region — Necessary for interaction with USP2
- Residue 470: Region — Necessary for interaction with USP2
- Residue 484: Region — Necessary for interaction with USP2
- Residue 485: Region — Necessary for interaction with USP2
- Residue 486: Region — Necessary for interaction with USP2
- Residue 487: Region — Necessary for interaction with USP2
- Residue 489: Region — Necessary for interaction with USP2
Pocket 3
- Residue 275: Region — Interaction with MTBP
- Residue 275: Region — Mediates interaction with RAD54B
- Residue 275: Region — ARF-binding
- Residue 275: Region — Region II
- Residue 276: Region — Interaction with MTBP
- Residue 276: Region — Mediates interaction with RAD54B
- Residue 276: Region — ARF-binding
- Residue 276: Region — Region II
- Residue 276: Region — Necessary for interaction with USP2
- Residue 277: Region — Interaction with MTBP
- Residue 277: Region — Mediates interaction with RAD54B
- Residue 277: Region — ARF-binding
- Residue 277: Region — Region II
- Residue 277: Region — Necessary for interaction with USP2
- Residue 278: Region — Interaction with MTBP
- Residue 278: Region — Mediates interaction with RAD54B
- Residue 278: Region — ARF-binding
- Residue 278: Region — Region II
- Residue 278: Region — Necessary for interaction with USP2
- Residue 279: Region — Interaction with MTBP
- Residue 279: Region — Mediates interaction with RAD54B
- Residue 279: Region — ARF-binding
- Residue 279: Region — Region II
- Residue 279: Region — Necessary for interaction with USP2
- Residue 280: Region — Interaction with MTBP
- Residue 280: Region — Mediates interaction with RAD54B
- Residue 280: Region — ARF-binding
- Residue 280: Region — Region II
- Residue 280: Region — Necessary for interaction with USP2
- Residue 282: Region — Interaction with MTBP
- Residue 282: Region — Mediates interaction with RAD54B
- Residue 282: Region — ARF-binding
- Residue 282: Region — Region II
- Residue 282: Region — Necessary for interaction with USP2
- Residue 428: Region — Necessary for interaction with USP2
- Residue 429: Region — Necessary for interaction with USP2
- Residue 429: Modified residue — Phosphoserine; by ATM
- Residue 430: Region — Necessary for interaction with USP2
- Residue 431: Region — Necessary for interaction with USP2
- Residue 449: Region — Necessary for interaction with USP2
- Residue 458: Region — Necessary for interaction with USP2
- Residue 486: Region — Necessary for interaction with USP2
- Residue 487: Region — Necessary for interaction with USP2
- Residue 488: Region — Necessary for interaction with USP2
- Residue 489: Region — Necessary for interaction with USP2
- Residue 490: Region — Necessary for interaction with USP2
- Residue 491: Region — Necessary for interaction with USP2
// Limitations & data provenance
Auto-populated from each section’s own status — not hand-maintained.