STRC h09 Phase 4k Fibril Actin Geometry
Phase 4k INCONCLUSIVE: tandem proxies show 4 geometric WH2-actin contacts, but 0 confidence-supported contacts across all 5 AF3 jobs.
Problem
Phase 4k tested whether AF3 could support the Phase 4j avidity requirement that multiple WH2 motifs can contact actin in the same local fibril/filament patch. The pre-registered cheap gate was N>=4 simultaneous WH2-actin engagements in at least one construct.
Method
- Script:
hypotheses/h09-hydrogel/scripts/phase4k_af3_contact_parser.py - Inputs: five AlphaFold Server ZIPs in
models/af3_results/h09_phase4k_4m_2026-04-27/ - Artifact:
hypotheses/h09-hydrogel/artifacts/phase4k_contact_parse_2026-04-27.json - Contact rule: WH2 motif heavy atom within 5.0 A of actin.
- Confidence rule: contact plus chain-pair ipTM >= 0.20.
Results
| Job | ipTM | pTM | Geometric WH2-actin contacts | Confidence-supported contacts | Gate |
|---|---|---|---|---|---|
| construct x2 + actin x3 | 0.45 | 0.57 | 0 | 0 | FAIL |
| construct x3 + actin x3 | 0.41 | 0.53 | 2 | 0 | FAIL |
| construct x4 + actin x3 | 0.37 | 0.49 | 0 | 0 | FAIL |
| tandem WH2 x4 + actin x3 | 0.57 | 0.68 | 4 | 0 | geometric-only |
| tandem WH2 x4 + actin x5 | 0.72 | 0.76 | 4 | 0 | geometric-only |
The final x4 construct was slow on AFS: the original row eventually completed and was downloaded; the duplicate recovery row was still running when the original result became available.
Verdict
- Outcome: INCONCLUSIVE
- Key numbers: any geometric pass = true; any confidence-supported pass = false; all WH2-actin chain-pair ipTM values remain below the 0.20 confidence floor.
- Interpretation: AF3 can place tandem WH2 motifs close to actin in raw coordinates, but the model does not support those contacts with chain-pair confidence. The high tandem x5 overall ipTM is therefore dominated by actin-actin assembly, not trusted WH2-actin placement.
- Limitations: AF3 is weak for short-motif actin side binding. Phase 4k should be treated as a negative-control/geometry caution, not as a falsification of the Phase 4m Kd soft-floor result.
Ranking delta
- Hypothesis h09: tier S → S | mech 5 → 5 | deliv 4 → 4 | misha_fit 3 → 3
- Evidence: Phase 4k does not independently close the N>=4 geometry gate, but Phase 4m already closed the higher-priority Kd_mono gate.
- Next step changes to: Phase 4l remains optional unless a paper-grade C_eff estimate is needed.
Connections
[part-of]h09 hub[supports]STRC h09 Phase 4m Kd Mono Soft Floor Result 2026-04-27[see-also]STRC h09 Phase 4j Avidity Kd Model 2026-04-26