// 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.

Rank 1 Rank 2 Rank 3

// Sequence

MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP
Length491 aa
UniProtQ00987
Mean structure confidence0.6258
Pocket clusters3
Numbering cross-walk94/491 vs. 6Q9L

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

cautionNumbering cross-walk against 6Q9L only mapped 94/491 residues (19%) — 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

zf-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 data

74 total structures in family · 8 distinct ligand scaffolds curated

  • 13SYW2J
  • 13SQU0P
  • 13SLJHP
  • 13STA1H9V
  • 13SWA1AJM

Conservation

returned data

309 seed sequences · mean pairwise identity 29.4%

Similar known proteins

returned data
  • 3T6P4.4% identity · (none)
  • 9SA10.0% identity · (none)
  • 9SA20.0% identity · (none)
  • 6SQP0.0% identity · (none)
  • 13SY0.0% 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_structure

8 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 data

Residue numbers below are pipeline-sequential, with the literature (author-deposited PDB 6Q9L) number shown in parentheses — 94/491 residues cross-walked.

RankPersistenceResidues
#1123(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(?) …
#21263(?), 266(?), 268(?), 270(?), 271(?), 272(?), 273(?), 274(?), 275(?), 276(?), 462(?), 463(?), 466(?), 467(?), 469(?), 470(?), 484(?), 485(?), 486(?), 487(?) …
#31275(?), 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: RegionNecessary for interaction with USP2
  • Residue 23: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 24: RegionNecessary for interaction with USP2
  • Residue 24: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 25: RegionNecessary for interaction with USP2
  • Residue 25: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 26: RegionNecessary for interaction with USP2
  • Residue 26: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 49: RegionNecessary for interaction with USP2
  • Residue 49: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 50: RegionNecessary for interaction with USP2
  • Residue 50: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 51: RegionNecessary for interaction with USP2
  • Residue 51: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 94: RegionNecessary for interaction with USP2
  • Residue 94: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 95: RegionNecessary for interaction with USP2
  • Residue 95: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 96: RegionNecessary for interaction with USP2
  • Residue 96: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 97: RegionNecessary for interaction with USP2
  • Residue 97: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 98: RegionNecessary for interaction with USP2
  • Residue 98: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 100: RegionNecessary for interaction with USP2
  • Residue 100: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 101: RegionNecessary for interaction with USP2
  • Residue 101: RegionSufficient to promote the mitochondrial pathway of apoptosis
  • Residue 104: RegionNecessary for interaction with USP2
  • Residue 190: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 190: RegionInteraction with MTBP
  • Residue 190: Modified residuePhosphoserine
  • Residue 191: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 191: RegionInteraction with MTBP
  • Residue 192: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 192: RegionInteraction with MTBP
  • Residue 193: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 193: RegionInteraction with MTBP
  • Residue 194: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 194: RegionInteraction with MTBP
  • Residue 195: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 195: RegionInteraction with MTBP
  • Residue 196: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 196: RegionInteraction with MTBP
  • Residue 197: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 197: RegionInteraction with MTBP
  • Residue 198: RegionInteraction with PYHIN1 and necessary for interaction with RFFL and RNF34
  • Residue 198: RegionInteraction with MTBP

Pocket 2

  • Residue 263: RegionInteraction with MTBP
  • Residue 263: RegionMediates interaction with RAD54B
  • Residue 263: RegionARF-binding
  • Residue 263: RegionRegion II
  • Residue 263: RegionDisordered
  • Residue 266: RegionInteraction with MTBP
  • Residue 266: RegionMediates interaction with RAD54B
  • Residue 266: RegionARF-binding
  • Residue 266: RegionRegion II
  • Residue 266: RegionDisordered
  • Residue 268: RegionInteraction with MTBP
  • Residue 268: RegionMediates interaction with RAD54B
  • Residue 268: RegionARF-binding
  • Residue 268: RegionRegion II
  • Residue 268: RegionDisordered
  • Residue 270: RegionInteraction with MTBP
  • Residue 270: RegionMediates interaction with RAD54B
  • Residue 270: RegionARF-binding
  • Residue 270: RegionRegion II
  • Residue 270: RegionDisordered
  • Residue 271: RegionInteraction with MTBP
  • Residue 271: RegionMediates interaction with RAD54B
  • Residue 271: RegionARF-binding
  • Residue 271: RegionRegion II
  • Residue 271: RegionDisordered
  • Residue 272: RegionInteraction with MTBP
  • Residue 272: RegionMediates interaction with RAD54B
  • Residue 272: RegionARF-binding
  • Residue 272: RegionRegion II
  • Residue 272: RegionDisordered
  • Residue 273: RegionInteraction with MTBP
  • Residue 273: RegionMediates interaction with RAD54B
  • Residue 273: RegionARF-binding
  • Residue 273: RegionRegion II
  • Residue 273: RegionDisordered
  • Residue 274: RegionInteraction with MTBP
  • Residue 274: RegionMediates interaction with RAD54B
  • Residue 274: RegionARF-binding
  • Residue 274: RegionRegion II
  • Residue 274: RegionDisordered
  • Residue 275: RegionInteraction with MTBP
  • Residue 275: RegionMediates interaction with RAD54B
  • Residue 275: RegionARF-binding
  • Residue 275: RegionRegion II
  • Residue 276: RegionInteraction with MTBP
  • Residue 276: RegionMediates interaction with RAD54B
  • Residue 276: RegionARF-binding
  • Residue 276: RegionRegion II
  • Residue 276: RegionNecessary for interaction with USP2
  • Residue 462: RegionNecessary for interaction with USP2
  • Residue 463: RegionNecessary for interaction with USP2
  • Residue 466: RegionNecessary for interaction with USP2
  • Residue 467: RegionNecessary for interaction with USP2
  • Residue 469: RegionNecessary for interaction with USP2
  • Residue 470: RegionNecessary for interaction with USP2
  • Residue 484: RegionNecessary for interaction with USP2
  • Residue 485: RegionNecessary for interaction with USP2
  • Residue 486: RegionNecessary for interaction with USP2
  • Residue 487: RegionNecessary for interaction with USP2
  • Residue 489: RegionNecessary for interaction with USP2

Pocket 3

  • Residue 275: RegionInteraction with MTBP
  • Residue 275: RegionMediates interaction with RAD54B
  • Residue 275: RegionARF-binding
  • Residue 275: RegionRegion II
  • Residue 276: RegionInteraction with MTBP
  • Residue 276: RegionMediates interaction with RAD54B
  • Residue 276: RegionARF-binding
  • Residue 276: RegionRegion II
  • Residue 276: RegionNecessary for interaction with USP2
  • Residue 277: RegionInteraction with MTBP
  • Residue 277: RegionMediates interaction with RAD54B
  • Residue 277: RegionARF-binding
  • Residue 277: RegionRegion II
  • Residue 277: RegionNecessary for interaction with USP2
  • Residue 278: RegionInteraction with MTBP
  • Residue 278: RegionMediates interaction with RAD54B
  • Residue 278: RegionARF-binding
  • Residue 278: RegionRegion II
  • Residue 278: RegionNecessary for interaction with USP2
  • Residue 279: RegionInteraction with MTBP
  • Residue 279: RegionMediates interaction with RAD54B
  • Residue 279: RegionARF-binding
  • Residue 279: RegionRegion II
  • Residue 279: RegionNecessary for interaction with USP2
  • Residue 280: RegionInteraction with MTBP
  • Residue 280: RegionMediates interaction with RAD54B
  • Residue 280: RegionARF-binding
  • Residue 280: RegionRegion II
  • Residue 280: RegionNecessary for interaction with USP2
  • Residue 282: RegionInteraction with MTBP
  • Residue 282: RegionMediates interaction with RAD54B
  • Residue 282: RegionARF-binding
  • Residue 282: RegionRegion II
  • Residue 282: RegionNecessary for interaction with USP2
  • Residue 428: RegionNecessary for interaction with USP2
  • Residue 429: RegionNecessary for interaction with USP2
  • Residue 429: Modified residuePhosphoserine; by ATM
  • Residue 430: RegionNecessary for interaction with USP2
  • Residue 431: RegionNecessary for interaction with USP2
  • Residue 449: RegionNecessary for interaction with USP2
  • Residue 458: RegionNecessary for interaction with USP2
  • Residue 486: RegionNecessary for interaction with USP2
  • Residue 487: RegionNecessary for interaction with USP2
  • Residue 488: RegionNecessary for interaction with USP2
  • Residue 489: RegionNecessary for interaction with USP2
  • Residue 490: RegionNecessary for interaction with USP2
  • Residue 491: RegionNecessary for interaction with USP2

// 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