STRC Research

STRC Computational Scripts Inventory

30 min read

STRC Computational Scripts Inventory

Registry of Python/shell scripts we wrote in ~/STRC/models/ that drive hand-built proofs. Distinct from STRC E1659A Computational Tool Audit — that catalogues 143 third-party prediction tools (AlphaMissense, REVEL, MaxEntScan, etc.) used for variant interpretation. Scripts here are “atoms of computation”; third-party tools they call are “instruments”.

Counts as of 2026-04-23:

  • 71 .py scripts in ~/STRC/models/
  • 4 .py scripts in ~/STRC/ (root — RBM24 scans + iCloud duplicates)
  • 38 JSON outputs (one per finished proof + a few per multi-output scripts)
  • 12 PNG figures
  • 1 SQLite catalog (third-party tools, separate from this inventory)

Status legend

  • active — currently produces results that drive a tier-S/A/B hypothesis
  • superseded — a newer script replaces it (note replacement in the row)
  • scaffold — TODO body only, never run end-to-end
  • orphan — was used once, no longer referenced; candidate for removal
  • duplicate — iCloud sync conflict ( 2.py suffix); should be removed but not auto-deleted

h01 — Pharmacochaperone E1659A (A-tier) | h01 hub

ScriptStatusOutputBacksLast successful run
pharmacochaperone_target_prep.pyactivepharmacochaperone_target_prep.json, .pngSTRC Pharmacochaperone Virtual Screen E1659A (Phase 0)2026-04-20
pharmacochaperone_phase1_mutant_pocket.pyactivepharmacochaperone_phase1_results.json, phase1_pocket_{WT,MUT}.pdb, .pngSTRC Pharmacochaperone Virtual Screen E1659A (Phase 1)2026-04-20 (docstring audit 2026-04-25)
pharmacochaperone_phase1b_highconf_realign.pyactivepharmacochaperone_phase1b_results.json, .pngSTRC Pharmacochaperone Virtual Screen E1659A (Phase 1B)2026-04-20
pharmacochaperone_phase2_pocket_scan.pyactivepharmacochaperone_phase2_results.json, phase2_top_pocket.pdb, .pngSTRC Pharmacochaperone Virtual Screen E1659A (Phase 2)2026-04-20 (docstring audit 2026-04-25)
pharmacochaperone_phase2b_subpockets.pyactivepharmacochaperone_phase2b_results.json, phase2b_top_subpocket.pdb, .pngSTRC Pharmacochaperone K1141 Fragment Pocket2026-04-20 (docstring audit 2026-04-25)
pharmacochaperone_phase3a_pharmacophore.pyactivepharmacochaperone_phase3a_pharmacophore.jsonSTRC Pharmacophore Model K1141 Pocket2026-04-20
pharmacochaperone_phase3b_virtual_screen.pyactivepharmacochaperone_phase3b_virtual_screen.jsonSTRC Pharmacochaperone Virtual Screen Ranked Leads2026-04-20 (docstring audit 2026-04-25)
pharmacochaperone_phase3c_shape_fit.pyactivepharmacochaperone_phase3c_shape_fit.jsonSTRC Pharmacochaperone Virtual Screen Ranked Leads2026-04-20
pharmacochaperone_phase4_common.pyactive (lib)— (imported by 4a-4f)STRC Pharmacochaperone Phase 4 Plan2026-04-21
pharmacochaperone_phase4a_pocket_reproducibility.pyactivepharmacochaperone_phase4a_pocket_reproducibility.jsonSTRC Pharmacochaperone Phase 4a Pocket Reproducibility2026-04-21
pharmacochaperone_phase4b_vina_gnina_screen.pyactivepharmacochaperone_phase4b_vina_gnina_screen.json (+ docking_runs/)STRC Pharmacochaperone Phase 4b Smoke Test2026-04-21 (docstring audit 2026-04-25)
pharmacochaperone_phase4c_wt_decoy.pyactivepharmacochaperone_phase4c_wt_decoy.jsonSTRC Pharmacochaperone Phase 4c WT Decoy2026-04-21
pharmacochaperone_phase4d_k1141a_decoy.pysuperseded by pharmacochaperone_phase4d_k1141a_double_mutant_dock.py (pointed at Ultra-Mini × TMEM145 rather than full-length E1659A)—flagged in STRC Pharmacochaperone Phase 4 Plannever (scaffold)
pharmacochaperone_phase4c_v3b_wt_decoy.pyactivepharmacochaperone_phase4c_v3b_wt_decoy.json (+ docking_runs/4c_v3b/)STRC h01 Phase 4c-v3b WT Decoy on v3b YELLOW 2026-04-242026-04-24
pharmacochaperone_phase4d_k1141a_double_mutant_dock.pyactivepharmacochaperone_phase4d_k1141a_double_mutant_dock.json (+ docking_runs/4d/)STRC h01 Phase 4d K1141A Double-Mutant Decoy 2026-04-242026-04-24
pharmacochaperone_admet_triage.pyactivepharmacochaperone_admet_triage.csv (104 ADMET cols × 67 SMILES), pharmacochaperone_admet_triage.json (triage summary: 6 clean / 28 light / 33 heavy; ADMET-AI v2.0.1 via ADMET-AI)STRC h01 Phase 7 ADMET-AI Triage 2026-04-242026-04-24
af3_jobs_2026-04-24_phase7h_builder.pyactive (builder)af3_jobs_2026-04-24_phase7h/ (12 job JSONs: Mini-STRC 1075-1775 × 6 NSAID CCDs × 2 WT/mut; MANIFEST.json + FASTA; submission pending Google auth)STRC h01 Phase 7H AF3 Protein-Ligand Validation 2026-04-242026-04-24 (JSONs built; AF3 results pending 6-12 h)
pharmacochaperone_phase6c_herg_extension.pyactivepharmacochaperone_phase6c_herg_extension.json (28 ligands × hERG/8ZYO/XB7; 21/28 sub-10 µM hit; class liability on bicyclic-aromatic-COOH)STRC h01 Phase 6c hERG Extension 2026-04-242026-04-24
pharmacochaperone_phase5c_mutant_cryptic_pocket.pyactivepharmacochaperone_phase5c_mutant_cryptic_pocket.json (20 Phase 5d E1659A snapshots; K1141 pocket stable, RMSF ratio 0.89, void 645-770 ų; 10 alt cavities, largest 435 ų at 50 Šbut matched WT full-length MD missing)STRC h01 Phase 5c-Mutant Cryptic Pocket Scan 2026-04-242026-04-24
pharmacochaperone_apbs_wt_mut_pocket.pyactivepharmacochaperone_apbs_wt_mut_pocket.json + apbs_wt_mut/{wt_full,e1659a_mutant}/{pqr,dx} (APBS 3.4.1 nonlinear PBE; E1659A pocket +7.1 kT/e vs WT; Vina WT-bias is force-field artefact)STRC h01 Phase 5j APBS WT vs Mutant Pocket Electrostatics 2026-04-242026-04-24
pharmacochaperone_phase4i_apbs_pose_rescore.pyactiveartifacts/phase4i_apbs_rescore/{phase4i_apbs_rescore.csv, phase4i_apbs_rescore_deltas.csv, phase4i_apbs_rescore.json, pocket_align_{R,t}.npy} (APBS grid reuse + pocket-local Kabsch alignment + pose-transplant; 20/29 v3b YELLOW prefer mutant at same geometry, median Δφ +0.70 kT/e, ΔG_formal −0.43 kcal/mol vs Vina 0/29 WT-bias; Tier-4 cheap-cross-check of Phase 5j)STRC h01 Phase 4i APBS Pose-Transplant Rescore 2026-04-242026-04-24
pharmacochaperone_phase5k_ensemble_apbs.pyactiveapbs_phase5k_ensemble/snap_NNN/{chainA.pqr, apbs.in, snap_NNN_pot.dx} (20 APBS grids, one per Phase 5d mutant snapshot), artifacts/phase5k_ensemble_apbs/phase5k_ensemble_apbs.{csv,json} (pocket φ ensemble mean +5.99 ± 1.37 kT/e, 20/20 positive; PASS; confirms Phase 5j holds under MD dynamics; Tier-0 Stage A)STRC h01 Phase 5k Ensemble APBS on Phase 5d Mutant MD 2026-04-242026-04-24
pharmacochaperone_phase5k_stageb_pose_ensemble.pyactiveartifacts/phase5k_ensemble_apbs/phase5k_stageb_pose_ensemble.{csv,json}, phase5k_stageb_per_ligand.csv (400 pose×snap measurements via pocket-local Kabsch transplant; median Δφ +1.08 kT/e, 92% positive, ΔG_formal −0.67 kcal/mol; top-1 by ensemble Coulomb = 2-amino-quinoline-3 / Vina rank #8; Tier-0 Stage B)STRC h01 Phase 5k Ensemble APBS on Phase 5d Mutant MD 2026-04-242026-04-24
pharmacochaperone_phase8_v5_library.pyactiveartifacts/phase8_v5_library/phase8_v5_library.{csv,sdf,json} (60-ligand v5 library around 2-amino-quinoline-3 top-Coulomb scaffold; non-planar tails × CONHOH × extended R3 palette; MW 310-460, logP [−0.5, 2.9], sp3 0.30-0.52; hERG mitigation via logP reduction)STRC h01 Phase 8 v5 Library Coulomb-Aware Design 2026-04-242026-04-24
pharmacochaperone_phase8b_v5_dock_rescore.pyactivedocking_runs/8b_v5/{ligands,poses,logs}/, artifacts/phase8b_v5_dock_rescore/phase8b_v5_dock_rescore.{csv,json} (60/60 Meeko+Vina dock into static E1659A + pose-transplant ensemble APBS rescore; top combined v5__aq3__adamantyl__CONHOH__-Cl at −8.19 kcal/mol combined, logP 1.94, 95% ensemble-positive; new chemistry class distinct from v3b)STRC h01 Phase 8 v5 Library Coulomb-Aware Design 2026-04-242026-04-24
pharmacochaperone_phase8c_v5_admet_triage.pyactiveartifacts/phase8c_admet/{phase8c_admet_raw.csv, phase8c_admet_summary.csv, phase8c_admet_per_source.csv, phase8c_admet_summary.json} (ADMET-AI Chemprop ensemble on v5 top-20 + v3b refs; 12/20 v5 clean vs 0/10 v3b; verdict CLEAN_DELTA_VS_V3B; DILI dominates — all 1-naphthyl variants fail 93-95 pct)STRC h01 Phase 8c v5 ADMET-AI Triage 2026-04-242026-04-24
pharmacochaperone_phase5d_wt_md.pyactiveartifacts/phase5d_wt_snapshots/snap_{000..019}.pdb (2 ns WT STRC MD, AMBER14SB/TIP3P/OpenCL, 14043 s wall, 12.98 ns/day, 20 snapshots; matched to Phase 5d mutant)STRC h01 Phase 5k-WT Matched Ensemble APBS 2026-04-252026-04-25
pharmacochaperone_phase5k_wt_ensemble_apbs.pyactiveapbs_phase5k_wt_ensemble/snap_NNN/{chainA.pqr,apbs.in,snap_NNN_pot.dx} (20 WT APBS grids), artifacts/phase5k_wt_ensemble_apbs/{csv,json} (WT pocket φ mean +1.46±1.55 kT/e; matched-ensemble Δ(mut−wt)=+4.53±0.46 kT/e = −2.79±0.28 kcal/mol formal-anion preference; Welch p=6.9e-12, Cohen’s d=3.10; paper-ready specificity claim)STRC h01 Phase 5k-WT Matched Ensemble APBS 2026-04-252026-04-25
pharmacochaperone_phase8d_v5_2_library_expanded.pyactiveartifacts/phase8d_v5_2_library/phase8d_v5_2_library.{csv,sdf,json} (384 v5.2 candidates: 9 tails × 5 heads × 7 R3; drug-likeness filter MW<500 logP<5 HBA≤10 rotB≤10; 280 non-planar + 104 planar)Phase 8d v5.2 Library + Dock-Rescore 2026-04-25 (pending)2026-04-25
pharmacochaperone_phase8e_v5_2_dock_rescore.pyactivedocking_runs/8e_v5_2/{ligands,poses,logs}/, artifacts/phase8e_v5_2_dock_rescore/phase8e_v5_2_dock_rescore.{csv,json} (384/384 Meeko+Vina dock into static E1659A + top-3-anionic-atom centroid + pose-transplant ensemble APBS rescore; top combined −8.13 biphenyl__CONHSO2Me__-CN but ADMET-flagged; v5 v1 top-1 adamantyl__CONHOH__-Cl at #5 combined remains #1 ADMET-clean)STRC h01 Phase 8d 8e 8f v5.2 Library Design 2026-04-252026-04-25
pharmacochaperone_phase8f_v5_2_admet_triage.pyactiveartifacts/phase8f_v5_2_admet/phase8f_admet_{raw,summary}.csv + .json (ADMET-AI 10-gate triage on v5.2 top-30; 15/30 clean; 14-compound shortlist combined<−7.0 AND flag-free; 8 adamantyl + 4 1-indanyl + 2 4-F-biphenyl × 4 acid-head classes)STRC h01 Phase 8d 8e 8f v5.2 Library Design 2026-04-252026-04-25
pharmacochaperone_phase8g_v5_2_offtarget.pyactiveartifacts/phase8g_v5_2_offtarget/phase8g_offtarget_{raw,selectivity}.{csv,json} (42 Vina docks: 6 ligands × 7 Phase 6c off-targets; 0/6 pass 100× selectivity gate including v3b ref; Vina vdW-dominated scoring cannot discriminate polar K1141 pocket vs hydrophobic membrane-protein pockets — methodological caveat for paper, not real safety failure)STRC h01 Phase 8g v5.2 Off-Target Panel 2026-04-252026-04-25
scripts/phase8h_lite/druggability_score.pyactiveartifacts/phase8h_lite/result_01_druggability.md (Halgren SiteMap-style Python grid burial estimator — fpocket replacement after qhull bug; K1141 pocket V 1145 ų, phobic 0.61, philic 0.39, V_pocket/V_lig 2.75; aromatic-rich shell W1612/F1646/F1169/W1652)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/extract_k1141_region.pyactive (helper)e1659a_k1141_region.pdb (25 Å sphere extract around K1141 NZ for any tool needing local protein patch)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/rwm_permeability.pyactiveartifacts/phase8h_lite/result_02_rwm_permeability.md (Salt 2001 + Stokes-Einstein + Avdeef logP/TPSA + Henderson-Hasselbalch; lead P 7.6× TMPA → ~60% applied conc basal turn at 90 min; sensitivity to CONHOH pKa ±0.5 negligible)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/selectivity_charge_proxy.pyactive (inconclusive lite)artifacts/phase8h_lite/result_03_selectivity_scan.md (Vina-pose-anchored side-chain charge counts within 6 Å + 10 Å of lead CONHO⁻; Vina parked ligand at 7.5 Å from K1141 → mech-4 attractor missed; valid as lower-bound diagnostic only, true selectivity test requires APBS on enclosed off-target pockets)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/selectivity_pocket_scan.pyactive (inconclusive lite)artifacts/phase8h_lite/result_03_selectivity_scan.md (receptor-wide Lys/Arg pocket scan within 10 Å; off-target K/R clusters dominate naive count because channels have voltage-sensor / selectivity-filter K/R-rich regions; not directly comparable to enclosed K1141 pocket)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/pose_ensemble_stability.pyactiveartifacts/phase8h_lite/result_04_pose_stability.md (LIE substitute: K1141 NZ position SD 1.11 Å across 20 Phase 5d snapshots, lead CONHO⁻↔NZ 5.02 ± 0.57 Å — Vina pose ensemble-stable in Coulomb attraction range; APBS-correct mode would tighten to 3 Å salt-bridge)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase8h_lite/tanimoto_ototoxins.pyactiveartifacts/phase8h_lite/result_05_tanimoto.md (RDKit Morgan FP r=2 2048 bits; lead vs 12-compound ototoxin panel from Schacht 2008; max Tanimoto 0.127 vs aspirin, threshold 0.40 → NO ototoxin motif overlap; aminoglycoside class max 0.086)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-262026-04-26
scripts/phase7i_tier1_pose_ensemble.pyactiveartifacts/phase7i_v52_combined/tier1_pose_stability.{md,csv} (K1141 NZ ↔ ligand-O min distance across 20 Phase 5d MD snapshots for 4 Tier-1 + reference; 2 Tier-1 in salt-bridge zone < 4 Å (4-F-biphenyl-phosphonate-CN 2.83 Å, adamantyl-CONHOMe-Cl 3.89 Å) — tighter than reference 5.02 Å; mech-4 K1141 engagement carries through CONHOH→CONHOMe/phosphonate head swap)h01 log § 2026-04-26 01:5x2026-04-26
scripts/phase7i_tier1_admet_recheck.pyactiveartifacts/phase7i_v52_combined/tier1_admet_recheck.{md,csv} (lookup from Phase 8f v5.2 ADMET-AI panel for 4 Tier-1 + reference; 5/5 ADMET-clean, 0 flags each; CONHOMe-Cl best on hERG 75.9 + BBB 70.9; phosphonates lower BBB 12–26 [intratympanic OK per DR5])h01 log § 2026-04-26 01:5x2026-04-26
scripts/phase8h_lite/rwm_permeability_tier1.pyactiveartifacts/phase8h_lite/result_06_tier1_rwm_tanimoto.md (Phase 7I lead-pivot refresh: CONHOMe-Cl P 12.9× TMPA → topical-deliverable; CONHOMe-CN P 3.0× marginal; both phosphonate Tier-1 BLOCKED at pH 7.4 (di-anion, f_neutral ≈ 0, P 10⁻¹³ cm/s) → require prodrug strategy: bis-POM ester or cyclic phosphonate, cf. tenofovir disoproxil precedent; CONHOH ref unchanged 7.6× TMPA)Phase 8h-lite2026-04-26
scripts/phase8h_lite/tanimoto_ototoxins_tier1.pyactiveartifacts/phase8h_lite/result_06_tier1_rwm_tanimoto.md (RDKit Morgan FP on 4 Phase 7I Tier-1 + reference vs Schacht 2008 9-compound class panel; max Tanimoto 0.154 vs aspirin across all 5 compounds, threshold 0.40 → NO ototoxin motif on lead-pivot; aminoglycoside class max ≤ 0.09)Phase 8h-lite2026-04-26
scripts/phase7i_apbs_offtarget_conhome.pyactiveartifacts/phase7i_v52_combined/apbs_offtarget_conhome.json, apbs_offtarget_summary.md (APBS 3.4.1 + pdb2pqr 3.6.1, PARSE FF, NaCl 0.150 M, T=310 K; lead anion-O ⟨φ⟩ for adamantyl-CONHOMe-Cl: STRC +2.48, KCNQ4 +1.12, TRPM4 +6.12, TMEM16A +4.27, Cx50 −3.55 kT/e; head swap reduces TRPM4 anti-selectivity by 3.24 kT/e vs CONHOH; still fails strict +2 kT/e gate on TRPM4)h01 log § 2026-04-26 01:5x2026-04-26
scripts/phase7i_v52_combined_analyze.pyactiveartifacts/phase7i_v52_combined/v52_combined_results.{json,csv}, artifacts/phase7i_v52_combined/SUMMARY.md (Boltz-2 ligand_iptm Δ(mut−wt) over 12 paired ligands combining v52_top3 + v52_rest11; 4 mut-prefer / 5 WT-prefer / 3 tie; mean Δ = −0.007 ± 0.055, t = −0.43; head-group decomposition: CONHOMe +0.066, phosphonate +0.050, CONHOH −0.008 [tie], CONHSO2Me −0.043, COOH −0.062; lead adamantyl_CONHOH_-Cl is a tie [Δ = −0.017]; new top hit adamantyl_CONHOMe_-Cl Δ = +0.066)h01 log § 2026-04-26 01:3x2026-04-26
scripts/phase7h_v52_rest11_analyze.pysuperseded by phase7i_v52_combined_analyze.pyartifacts/phase7h_v52_rest11/v52_rest11_results.{json,csv} — single-batch v52_rest11 (9 paired ligands). Phase 7I combined merges with v52_top3 (12 paired) + adds head/body/ortho decomposition. Keep file for reproducibility; do not extend.h01 log § 2026-04-26 01:2x2026-04-26
scripts/phase7h_v52_top3_analyze.pysuperseded by phase7i_v52_combined_analyze.pyartifacts/phase7h_v52_top3/v52_top3_results.{json,csv} — single-batch v52_top3 (3 paired ligands). Phase 7I combined merges both batches and is canonical.h01 log § 2026-04-26 01:3x2026-04-26
scripts/phase8h_v53_phosphonate_ensemble.pysuperseded by phase7i_tier1_pose_ensemble.pyartifacts/phase8h_v53/v53_ensemble_distances.{json,csv} — 2-candidate Vina+ensemble check on 1-indanyl_phosphonate_-CF3 (min_d 4.39 ± 0.65 Å) + adamantyl_CONHOMe_-CN (2.63 ± 1.28 Å). Phase 7I tier-1 generalises to all 4 Tier-1 + reference with consistent prep; values differ from 7I (4.41 / 4.21 Å) due to conformer/seed. Keep for reproducibility; do not extend.h01 log § 2026-04-26 01:3x2026-04-26
scripts/phase8g_v2/apbs_offtarget_rescore.pyactiveartifacts/phase8g_v2_apbs_offtarget.json (APBS npbe mg-auto on 5 receptors with crystallographic metals retained; samples φ at lead’s hydroxamate-O atoms; STRC E1659A K1141 ref +2.51 kT/e vs TRPM4 +9.36 / TMEM16A +4.89 / KCNQ4 +0.91 / Cx50 −3.02; gate FAIL margin −6.85 kT/e; metals 17-62 Å from anion-O so failure mode is residue-driven Coulomb not Zn chelation; STRC pose anion-O sits below Phase 5k pocket-centre +5.99 kT/e — Vina pose sub-optimal for electrostatics)STRC h01 Phase 8g-v2 APBS Off-Target Rescore 2026-04-262026-04-26
scripts/phase5l_fragment_af3_builder.pyactive (scaffold, awaits AF3 upload)~/STRC/models/af3_jobs_2026-04-26_phase5l/{fragment_120,150,180,220}_{wt,e1659a}.json + manifest.json (8 AF3-server payloads for K1141 ±60/75/90/110-aa fragment ladder; selection gate pocket pLDDT ≥ 80 + K1141-ring Cα RMSD < 1.5 Å vs full-length; smallest-passing fragment becomes Phase 5m τRAMD substrate; cuts MD wall ~4× vs Phase 5d full-length)STRC K1141 Fragment Construct Strategy2026-04-26
scripts/phase5m_taramd_skeleton.pyscaffold— (skeleton awaiting Phase 5l winning fragment + ramd-openmm install; will run τRAMD 10×5 ns × 14 ligands for relative residence-time ranking; closes the k_off gap that all H01 phases to date have left open)Pharmacochaperone Residence Time Criterion, RAMD-OpenMM2026-04-26
pharmacochaperone_phase4e_offtarget_selectivity.pyactivepharmacochaperone_phase4e_offtarget_selectivity.jsonSTRC Pharmacochaperone Phase 4e Off-Target Selectivity2026-04-21
pharmacochaperone_phase4f_interface_rescue.pymethod-inadequatepharmacochaperone_phase4f_interface_rescue.jsonSTRC Pharmacochaperone Phase 4f Interface Rescue SMOKE2026-04-22 (SMOKE inconclusive)
pharmacochaperone_phase4g_repurpose_screen.pyactivepharmacochaperone_phase4g_repurpose_screen.jsonSTRC Pharmacochaperone Phase 4g Repurpose Screen2026-04-22
pharmacochaperone_phase5_md.pyscaffold—STRC Pharmacochaperone Phase 4 Plan (gate 7)never (docstring audit 2026-04-25)
pharmacochaperone_phase5a_apo_md_smoke.pyactivepharmacochaperone_phase5a_apo_md_smoke.json, artifacts/phase5a_snapshots/STRC h01 Phase 5 MD Ensemble Rescoring 2026-04-232026-04-23
pharmacochaperone_phase5b_ensemble_redock.pyactivepharmacochaperone_phase5b_ensemble_redock.jsonSTRC h01 Phase 5 MD Ensemble Rescoring 2026-04-232026-04-23
pharmacochaperone_phase5c_cryptic_pocket_detection.pyactivepharmacochaperone_phase5c_cryptic_pocket_detection.jsonSTRC h01 Phase 5c Cryptic Pocket Analysis 2026-04-232026-04-23
pharmacochaperone_phase3c_v2a_library_build.pyactivepharmacochaperone_phase3c_v2a_library_build.json, docking_runs/3c_v2/ligands/*.pdbqtSTRC h01 Phase 3c v2 Expanded Screen 2026-04-232026-04-23
pharmacochaperone_phase3c_v2b_ensemble_dock.pyactivepharmacochaperone_phase3c_v2b_ensemble_dock.jsonSTRC h01 Phase 3c v2 Expanded Screen 2026-04-232026-04-23
pharmacochaperone_phase3c_v3_fenamic_covalent_library.pyactivepharmacochaperone_phase3c_v3_fenamic_covalent_library.json, docking_runs/3c_v3/ligands/*.pdbqtSTRC h01 Phase 3c v3b Fenamic + Covalent Screen 2026-04-23 (pending)2026-04-23
pharmacochaperone_phase3c_v3b_ensemble_dock.pyactivepharmacochaperone_phase3c_v3b_ensemble_dock.json (0 GREEN / 29 YELLOW / 21 RED; ceiling Kd 4.57 µM)STRC h01 Phase 3c v3b + 5d Delivery 2026-04-242026-04-24
pharmacochaperone_phase5d_e1659a_md.pyactivepharmacochaperone_phase5d_e1659a_md.json, artifacts/phase5d_snapshots/snap_000-019.pdb (20 snaps, 2 ns, K1141+E1659A verified)STRC h01 Phase 3c v3b + 5d Delivery 2026-04-242026-04-23
pharmacochaperone_phase5e_mutant_ensemble_redock.pyactivepharmacochaperone_phase5e_mutant_ensemble_redock.json (max kd_ratio 2.09× → WT proxy validated; 0 GREEN / 0 YELLOW / 11 RED on mutant; best flufenamic Kd 32.7 µM, tafamidis-analog 51.3 µM)STRC h01 Phase 5e Mutant Re-Dock Delivery 2026-04-242026-04-24
pharmacochaperone_phase3c_v4_library.pyactivepharmacochaperone_phase3c_v4_library.json, docking_runs/3c_v4/ligands/*.pdbqt (1,572 ligands: 1,550 combinatorial on 3 locked cores + 22 Phase 4h seeds)STRC h01 Phase 3c v4 Fragment-Grow (running, write-up pending)2026-04-24
pharmacochaperone_phase3c_v4_ensemble_dock.pyactivepharmacochaperone_phase3c_v4_ensemble_dock.json (0 GREEN / 32 YELLOW / 18 RED of 1,572; top mean −7.27 Kd 4.65 µM f_PC 0.341; 92 min wall)STRC h01 Phase 3c v4 Fragment-Grow Delivery 2026-04-242026-04-24
pharmacochaperone_phase6c_offtarget_panel.pyactive (—prep + —dock 6/6 targets via verified bound-ligand PDBs: TRPM4 8RD9/A1H0C, Cx50-via-Cx36 8QOJ/YMZ, KCNQ4 7BYM/FBX, TMEM16A 7ZK3/JRF, COX-1 1Q4G/BFL, COX-2 5IKR/ID8; cif-fallback parser handles obabel HETATM stripping)pharmacochaperone_phase6c_targets.json (Stage A); pharmacochaperone_phase6c_offtarget_panel.json (Stage B 60 docks: tafamidis Kd 1.5 µM COX, 4.7 µM TMEM16A, 55 µM TRPM4, 461 µM KCNQ4; bicyclic-COOH bioisosteres ALL hit COX+TMEM16A sub-5 µM but cleanly de-select KCNQ4)STRC h01 Phase 6c Full 6-Target Panel 2026-04-242026-04-24
pharmacochaperone_phase6c_crossdock_v4.pyscaffold (executes the moment v4 ensemble dock JSON lands; extracts top-N v4 winners by mean ΔG, writes ligand panel JSON, invokes Phase 6c —dock with v4-derived selectivity reference)pharmacochaperone_v4_top_for_6c.json + populates pharmacochaperone_phase6c_offtarget_panel.json with selectivity_ratio(pending v4 verdict)never (waiting on v4)
scripts/phase8h_lite/cochlear_pbpk_ode.pyactiveartifacts/phase8h_lite/result_07_cochlear_pbpk.{json,md} (8-compartment PBPK ODE: DEPOT→MEC→PER_B↔PER_A↔ENDO→HC_CYT↔HC_ER + BLOOD; HC_ER Cmax 0.4–1.3 µM at 100 µM applied IT dose; default-apical fraction-time-above-1µM = 0%; eustachian-tube clearance ≈ 11 000× faster than RWM crossing → free-drug bottleneck; mass balance 100%)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-26 §7 · ELX-02 In Vitro Clinical PBPK Disconnect2026-04-26
scripts/phase8h_lite/k1141_interface_map.pyactiveartifacts/phase8h_lite/result_08_k1141_interface_map.{json,md} (Phase 5d full-length 1775-res snapshot; K1141 → central FN3-like, A1659 → C-terminal ZP-like, 13.91 Å apart; pocket-shell ≤ 12 Å = 47 residues; K1141 SASA-proxy 120, partially-buried; surface runs near K1141 ≤ 3 contiguous residues → no canonical partner-interface patch; CFTR F508del + Elexacaftor architectural analog)STRC h01 Phase 8h-lite Light Computational Evidence Package 2026-04-26 §8 · Migalastat Dosing-Cycle Principle2026-04-26
scripts/phase8g_v3_pocket_max_phi.pyactiveartifacts/phase8g_v3/pocket_max_phi.{json,md} (resamples existing Phase 8g-v2 / 7i APBS dx grids with solvent-accessibility mask 1.5–4.0 Å; pocket top-10% φ across 5 receptors × 2 lead variants; CONHOH FAIL margin −5.24 kT/e (STRC +29.95 ≤ TMEM16A +35.19); CONHOMe FAIL margin −2.49 kT/e (STRC +21.90 ≤ TRPM4 +24.39); FAIL is residue-driven not pose-driven on both variants → Phase 8g-v3 full re-dock STOPPED, τRAMD promoted P0)STRC h01 Phase 8g-v3-lite + 8h-lite 9 Pocket Max Phi + Dose Sweep 2026-04-262026-04-26
scripts/phase8h_lite/cochlear_pbpk_dose_sweep.pyactiveartifacts/phase8h_lite/result_09_pbpk_dose_sweep.{json,md} (PBPK dose-escalation × apical-uptake matrix: 100 µM / 1 mM / 10 mM × fast/default/slow apical t½; 1 mM IT closes therapeutic window across all apical brackets at 94-97 % time-HC_ER ≥ 1 µM with 0 % HC_CYT ≥ 50 µM cytosol safety breach; 10 mM = safety cliff 66-94 % cytosol breach in fast/default; 1 mM locked as new reference dose)STRC h01 Phase 8g-v3-lite + 8h-lite 9 Pocket Max Phi + Dose Sweep 2026-04-262026-04-26
scripts/phase5l_selection_gate.pyactiveartifacts/phase5l/selection_results.{json,md} (gemmi CIF parser; pocket pLDDT, K1141-ring Cα RMSD, whole-fragment RMSD vs Phase 5d snap_010 across 8 AF3 fragment-variants; strict gate FAIL on all [whole-frag-RMSD floor 4.87 Å — AF3 single-domain divergence]; relaxed gate ring-only fidelity → 151_e1659a winner: ring RMSD 0.97 Å, pocket pLDDT 78.7, pTM 0.65)STRC h01 Phase 5l + 5m Smoke Fragment AF3 + tauRAMD Pipeline 2026-04-262026-04-26
scripts/phase5m_taramd_smoke.pyactiveartifacts/phase5m_smoke/{smoke_fragment.pdb, smoke_ligand.sdf, smoke_system.xml, smoke_trajectory.dcd, smoke_ramd.log, smoke_log.csv, smoke_result.json} (τRAMD smoke on hand-truncated 151-aa Phase 5d fragment + lead adamantyl-CONHOMe-Cl; 45 714 atoms, OpenCL Metal, 14 kcal/mol/Å bias, 2 fs timestep; UNBOUND at MD step 8950 = 17.9 ps biased MD; ligand COM drift 4.07 nm to threshold; ~10 min wall total; 1-replica smoke validates pipeline, production needs 10 replicas/ligand for SEM)STRC h01 Phase 5l + 5m Smoke Fragment AF3 + tauRAMD Pipeline 2026-04-262026-04-26
scripts/phase5l_fragment_af3_builder.pyactive (executed 2026-04-26)~/STRC/models/af3_jobs_2026-04-26_phase5l/{strc_k1141_frag_{121,151,181,221}_{wt,e1659a}.json, manifest.json, submission_log.json, downloads/} (8 AF3 server JSON payloads + submission via alphafold-server skill in 2 min wall + 8 CIFs/40 models downloaded; submission_log.json maps each to AFS job ID + URL + local files)STRC h01 Phase 5l + 5m Smoke Fragment AF3 + tauRAMD Pipeline 2026-04-262026-04-26
scripts/phase5m_taramd_skeleton.pysuperseded by phase5m_taramd_smoke.py— (skeleton retained for reproducibility; documented original Phase 5m design intent before smoke surfaced operational lessons; do not extend)STRC h01 Phase 5l + 5m Smoke Fragment AF3 + tauRAMD Pipeline 2026-04-262026-04-26
scripts/phase5n_lite_nglyc_calnexin_map.pyactiveartifacts/phase5n_lite/result_nglyc_map.{json,md} (NX[ST] sequon map across 1775-aa STRC; 14 sequons total, 0 in C-terminal ZP-like 1501-1771 where E1659A lives, nearest sequon N1179@29.8 Å outside 25 Å calnexin engagement; E1659A creates 0 / destroys 0 sequons → calnexin extended-retention NEGATIVE as rate-limiting step candidate; reranks BiP/HRD1-SEL1L up)STRC h01 Phase 5n-lite Calnexin Retention NEGATIVE 2026-04-262026-04-26
scripts/phase5p_v53_weakanion_library.pyactiveartifacts/phase5p/v53_library.{csv,json,md} (12 v5.3 acyl-sulfonamide candidates: 2 heads × 2 bodies × 3 tails; 6/12 PASS Lipinski + TPSA ≤ 100 + ≤ 1 anion gates; top-3 next-gen 1-indanyl_acylsulfonamide_SO2Me_-Cl MW 415.9, adamantyl_acylsulfonamide_SO2Me_-Cl MW 434.0 [direct head-swap of v5.2 lead], adamantyl_acylsulfonamide_SO2Me_-CF3 MW 467.5; activation gated on Phase 5m STRC:TRPM4 τ-ratio < 5×)STRC h01 Phase 5p v53 Acyl Sulfonamide Library 2026-04-262026-04-26
scripts/phase5m_taramd_production.pyactiveartifacts/phase5m_production/{fragment_5d_truncated_e1659a.pdb, per_ligand/<lig>/{system.xml, equilibrated_state.xml, topology.pdb, replica_<k>/{ramd.log, trajectory.dcd, result.json}}, ranking.{json,md}} (5 v5.2 ligands × 5 replicas on Phase-5d-truncated 151-aa K1141 fragment, all 25 replicas UNBOUND in 13-55 ps biased MD; final τ̄: CONHOMe-CN 26.1 / 4-F-biphenyl-phosphonate-CN 21.1 / CONHOMe-Cl LEAD 19.6 / 1-indanyl-phosphonate-CF3 19.0 / CONHOH mech-anchor 15.4 ps; within-STRC spread 1.7× falsifies same-head kinetic-selectivity rescue → v5.3 pipeline activated; subprocess-per-replica with 30-min wall-cap, parent-side log parse, single-call run_RAMD_sim, Gasteiger charges; 5 SIGSEGV/parser-race bugs debugged)STRC h01 Phase 5m Production tauRAMD Ranking 2026-04-262026-04-26
scripts/phase5m_aggregate_completed.pyactiveartifacts/phase5m_production/aggregate_partial.{json,tsv} (read-only roll-up of all per_ligand/<lig>/replica_*/result.json; produces per-ligand n_done / n_unbound / n_censored / median+mean+min+max τ_ps; safe to run while production is alive — no writes inside per_ligand/)STRC h01 Phase 5m Production tauRAMD Ranking 2026-04-262026-04-26
scripts/phase5e_v2_mutant_redock.pyactive (running 2026-04-26 — 3 BG re-runs in flight + B-lite-v3 finished)artifacts/phase5e_v2/<source>/{aggregate.json, aggregate.tsv, ligands/<lig>.pdbqt, docking/<lig>__snap_NNN.{pdbqt,log}} (generic mutant-ensemble Vina re-dock against 20 Phase 5d snapshots; same K1141 pocket box 18×18×18 Å on residues 1141/1135/1137/1165/1167/1175 Cα centroid as Phase 5e; receptor PDBQT via obabel -xr --partialcharge gasteiger. 2026-04-26 patch (Phase 5e-v3): ligand SMILES → PDBQT via dimorphite-DL pH 7.4 protonation → meeko PDBQT writer — fixes Gasteiger zero-anion artifact (verified phosphonate dianion = −2.000 e); fallback to obabel/Gasteiger if meeko fails on a given molecule. Sources: v3b-top50 (Phase 3c v3b stage2, 50 lig × 20 snap, 1000 dockings ~3-4h), v5.2 (full 384-lig library, ~21h overnight), v5.2-shortlist (5 τRAMD lig, ~10 min), v5.3-pass (Phase 5p PASS-list 6 lig), v5.3-top3 (h01 hub-prioritised 3 acyl-sulfonamides, complements Boltz-2 5q batch). Writes outputs INSIDE STRC vault — replaces stale ~/Brain/research/strc/models WORK_DIR. Finding 2026-04-26 11:5x: B-lite-v3 (formal-charge full 20-snap) Spearman ρ(Vina ΔG, −τRAMD median) = −0.9 (was −1.0 with Gasteiger) — anti-correlation persists → rigid-receptor protocol is the load-bearing artifact, not partial charges.STRC h01 Phase 5e-v2 v5.2 Shortlist Vina vs tauRAMD 2026-04-262026-04-26
scripts/phase5e_v2_partial_wt_vs_mut.pyactiveartifacts/phase5e_v2/v3b-top50/partial_wt_vs_mut.{json,tsv} (early WT→mut shift extractor; reads latest ~/STRC/logs/phase5e_v2_v3b_top50_*.log, parses per-ligand ΔG runs in flight, joins to Phase 3c v3b stage2_results WT mean_dG; produces directional ΔΔG signal with caveat that n=1/snap is noisy. Used 2026-04-26 to surface the early “11/13 weaker on mutant” trend that was later traced to Gasteiger zero-anion artifact and re-interpreted post-Phase 5e-v2 update.)STRC h01 Phase 5e-v2 v5.2 Shortlist Vina vs tauRAMD 2026-04-262026-04-26
models/boltz_jobs_2026-04-26_phase5q_v53/inputs/{v5.3__aq3__*.yaml} (3 jobs) + aggregate.{json,tsv}active (delivered 2026-04-26 04:31 UTC, 23:14 wall on M5 MPS)models/boltz_jobs_2026-04-26_phase5q_v53/{inputs/*.yaml, results/boltz_results_inputs/predictions/<lig>/{*.cif, confidence_*_model_{0..4}.json}, aggregate.{json,tsv}, MANIFEST.json} (Boltz-2 v2.2.1 protein-ligand cofold on STRC mini-fragment 701-aa × 3 v5.3 acyl-sulfonamide top-3 with dimorphite-DL pH 7.4 deprotonated SMILES [CS(=O)(=O)[N-]C(=O)...]; 5 diffusion samples per ligand, 0 failed. All 3 PASS ipTM ≥0.50. Best: 1-indanyl_acylsulfonamide_SO2Me_-Cl ipTM 0.645 / pTM 0.855 / 5-seed mean 0.578±0.056. Tightest σ: adamantyl_acylsulfonamide_SO2Me_-Cl σ=0.034. Phase 5q proof note delivered: Boltz-2 + Vina-v3 rigid AGREE on rank-1 = 1-indanyl_SO2Me_-Cl — opposite of Phase 5e-v2 v5.2 phosphonate finding (Vina vs τRAMD anti-correlated on dianion). Method agreement contingent on anion charge magnitude (−1 sulfonamide vs −2 phosphonate).)STRC h01 Phase 5q v5.3 Acyl Sulfonamide Boltz-2 + Vina Consensus 2026-04-262026-04-26
scripts/phase5m_trpm4_taramd.pyactive (DELIVERED 2026-04-26 14:50 UTC, PID 45852 exited cleanly after 2 lig × 3 replicas = 6 runs, ~2h M5 Metal)artifacts/phase5m_trpm4/{trpm4_8rd9_chainA_fixed.pdb (PDBFixer-treated 606-aa monomer of TRPM4 8RD9 chain A, 4914 atoms), per_ligand/<lig>/{system.xml, equilibrated_state.xml, topology.pdb, replica_<k>/{ramd.log, trajectory.dcd, result.json}}, ranking.{json,md}, partial_status.md, paper_figure3.{png,svg}} (cross-target τRAMD; clones Phase 5m production with 3 substitutions: SNAP→8RD9_stripped.pdb chain A, USE_PHASE5D_TRUNC=False with PDBFixer hydrogen-add, DOCK_POSES→docking_runs/6c_offtarget/TRPM4/poses_8g/. 2 ligands [adamantyl_CONHOMe_-Cl LEAD + adamantyl_CONHOH_-Cl mech-anchor — only Phase 5m candidates with existing TRPM4 8RD9 docked poses] × 3 replicas = 6 runs total. Result: τ_TRPM4 / τ_STRC = 1.08-1.52×, both FAIL Phase 5p gate >5×. Replica_02 LEAD outlier τ=53.4 ps suggests TRPM4 metastable secondary mode. Caveat: trajectory DCD reporter only writes on displacement events, gave 1-5 frames per replica — insufficient for residue-contact analysis until re-run with 100-step interval.)STRC h01 Phase 5m TRPM4 Cross-Target tauRAMD 2026-04-262026-04-26
scripts/phase5m_paper_figure3_taramd.pyactive (executed 2026-04-26 15:05 UTC)artifacts/phase5m_trpm4/paper_figure3.{png,svg} (3-panel matplotlib figure: Panel A = STRC τRAMD per-ligand × 5 with median bars + per-replica scatter; Panel B = TRPM4 τRAMD × 2 with replica_02 outlier visible at 53 ps; Panel C = ratio bars + Phase 5p gate horizontal line at 5× + parity at 1×. Reads aggregate JSON files, no new compute.)STRC h01 Phase 5m TRPM4 Cross-Target tauRAMD 2026-04-26 (Figure 3)2026-04-26
scripts/phase5m_trpm4_replica_analysis.pybroken — needs fix next session (ran 2026-04-26 15:01 UTC; output written but analysis inconclusive)artifacts/phase5m_trpm4/replica_02_metastable_analysis.{json,md} (intended residue-contact comparator across 3 LEAD replicas to identify TRPM4 anti-target residues; FAILED on two issues: (a) Phase 5m DCD reporter triggers on displacement events not regular intervals, gave 1/1/5 frames — too sparse; (b) atom-filter logic cherry-picks non-standard residue names from solvent, giving spurious min-distances ~181 Å. Fix: (i) tighten filter to chain.id=='A' AND residue.name in STANDARD_AA_3; (ii) re-run TRPM4 τRAMD replica_02 with DCD interval 100 steps for 540-frame dense trajectory.)(will back paper Figure 3 mechanism panel after fix)2026-04-26
scripts/phase5e_v2_paper_figure2.pyactive (executed 2026-04-26 15:18 UTC)artifacts/phase5e_v2/paper_figure2.{png,svg} (3-panel matplotlib figure: Panel A = Gasteiger-blind v5.2 phosphonate scatter [archived smoke, n=1 → ρ=NaN, placeholder text]; Panel B = formal-charge v5.2 phosphonate scatter ρ=−0.7 still inverted; Panel C = v5.3 sulfonamide Vina×Boltz-2 scatter, methods AGREE. Title encodes the chemistry-class rule: anion ≥−1.5 → AGREE, ≤−2 → INVERT. Reads aggregate JSON, no compute.)STRC h01 Phase 5e-v2 v5.2 Shortlist Vina vs tauRAMD 2026-04-26 (Figure 2) + STRC h01 Phase 5q v5.3 Acyl Sulfonamide Boltz-2 + Vina Consensus 2026-04-262026-04-26
scripts/phase5q_strc_dock_v53.shscaffold (next-session execution pending)models/docking_runs/8e_v5_3/poses/{v5.3__aq3__*acylsulfonamide*.pdbqt} (Vina exh=16 dock of v5.3 top-3 onto STRC E1659A snap_010 receptor PDBQT, K1141 pocket-ring centroid box from phase5e_v2/v5_2-shortlist/docking/snap_010_box.json. ~10 min. Step 1 of v5.3 within-target τRAMD pipeline.)(lemma pre-screen path)2026-04-26
scripts/phase5q_strc_taramd_v53.pyDELIVERED 2026-04-26 20:00 UTC (~14 min wall on M5 Max CPU OpenMM, all 15/15 UNBOUND in 7.1–22.3 ps biased MD)artifacts/phase5q_strc_v53/{per_ligand/<lig>/{system.xml, equilibrated_state.xml, topology.pdb, replica_<k>/{ramd.log, trajectory.dcd, result.json}}, ranking.{json,md}} (Phase 5m clone with v5.3 LIGANDS + DOCK_POSES → 8e_v5_3/poses + OUT → phase5q_strc_v53. Within-target σ_within = 1.45× (max/min τ̄). Lemma gate triggered: σ < 3× → cross-target STRC:TRPM4 mathematically bounded ≤ 2.9× ≪ 5× → v5.3 kinetic-selectivity rescue falsified pre-emptively; TRPM4 v5.3 dock/τRAMD SKIPPED (~3h saved). Bug fix: f-string {u:.1f if u else '—'} invalid; replaced with temp var u_str. Also created models/docking_runs/8e_v5_3/poses/ symlinks → phase5e_v2/v5_3-top3/ligands/*.pdbqt so DOCK_POSES resolves.)STRC h01 Phase 5q v5.3 STRC Within-Target tauRAMD 2026-04-262026-04-26
scripts/phase5q_paper_figure4_v53_pre_emptive.pyDELIVERED 2026-04-26 20:25 UTCartifacts/phase5q_strc_v53/paper_figure4.{png,svg} (2-panel matplotlib: Panel A = v5.3 STRC τRAMD per-ligand mean ± SEM bars + per-replica scatter, within-target σ annotated; Panel B = lemma cross-target bound 2.9× vs required 5× gate, σ_within ≥ 3× threshold overlay. Reads ranking.json. No new compute, ~2 s.)STRC h01 Phase 5q v5.3 STRC Within-Target tauRAMD 2026-04-26 + STRC Paper Draft Outline 2026-04-25 §4.62026-04-26
scripts/phase9b_lite_residue_field_decomposition.pyDELIVERED 2026-04-27 11:29 HKTartifacts/phase9b_lite_residue_field/{phase9b_lite_residue_field.json, radius_summary.csv, per_snapshot_radius_fields.csv, phase9b_lite_residue_field.md} (APBS-free residue-field smoke on matched n=20 WT Phase 5a + n=20 E1659A Phase 5d snapshots; formal charged side-chain representatives around K1141-ring centroid. Broad shells support E1659A>WT sign: 18 A delta +0.181 q/A, paired p=1.54e-10; 12-24 A positive. 9 A inner shell opposes, so mechanism is wide charged-neighbourhood, not uniformly positive microenvironment. Not production MM-PBSA.)STRC h01 Phase 9b-lite Residue Field Decomposition 2026-04-272026-04-27
scripts/phase9b_mmpbsa_smoke.pyDELIVERED 2026-04-27 11:54 HKT — TOOLING_READY_INPUTS_BLOCKEDartifacts/phase9b_mmpbsa_smoke/{phase9b_mmpbsa_smoke.json, phase9b_mmpbsa_smoke.md} (Phase 9b preflight: probes GROMACS, gmx_MMPBSA, MMPBSA.py, cpptraj, tleap, antechamber; inventories h01 topology inputs; attempts Phase 5q E1659A OpenMM holo → Amber path. Result: tools callable, but no matched WT holo v5.3 input and no native GROMACS/Amber topology files; ParmEd conversion blocked by 37,405 bonds without Amber bond types. No MM-PBSA sign produced.)STRC h01 Phase 9b MM-PBSA Tooling Preflight 2026-04-272026-04-27
scripts/phase9b_matched_holo_input_builder.pyDELIVERED 2026-04-27 14:13 HKT — DOCKED_POSE_CHARGE_REPAIRED_MINIMIZED_SMOKE_PASSartifacts/phase9b_matched_holo_inputs/{phase9b_matched_holo_inputs.json, phase9b_matched_holo_inputs.md, wt/, e1659a/} + artifacts/phase9b_geometry_sanity/{phase9b_geometry_sanity.json, phase9b_geometry_sanity.md} (repaired Phase 9b matched WT/E1659A Amber inputs for v5.3 adamantyl acyl-sulfonamide-Cl on snap_010. Source pose is now the full-length Phase 5e-v2 Vina PDBQT, not the Phase 5q centroid-only τRAMD SDF; Meeko/Vina formal-charge PDBQT charges are patched into GAFF2 mol2, ligand charge sum −1.000000. tleap PASS for both. Raw WT still has one 1.167 A O—O contact and raw WT MM-GBSA is invalid; 80-step restrained minimization removes all heavy-heavy contacts <2.5 A in both WT/E1659A. Minimized one-frame MM-GBSA smoke: WT DELTA TOTAL −13.03, E1659A −17.79 kcal/mol; compatibility smoke only, not production binding estimate.)STRC h01 Phase 9b Matched Amber Input Compatibility 2026-04-272026-04-27
scripts/phase9b_minrelax_multiframe_smoke.pyDELIVERED 2026-04-27 14:38 HKT — MINRELAX_MULTIFRAME_SMOKE_SUPPORTIVEartifacts/phase9b_minrelax_multiframe_smoke/{phase9b_minrelax_multiframe_smoke.{json,md}, wt/, e1659a/} (reuses repaired matched WT/E1659A Amber inputs, runs 60 extra implicit-GB minimization steps with protein restrained and ligand free, writes 6 frames per condition, then rescored with MMPBSA.py GB. WT DELTA TOTAL -15.84 +/- 0.46 SEM; E1659A -18.18 +/- 0.09; E1659A-minus-WT -2.35 kcal/mol. Robustness smoke only; production explicit-solvent holo MD / MM-PBSA still pending.)STRC h01 Phase 9b Min-Relax Multi-Frame MM-GBSA Smoke 2026-04-272026-04-27
scripts/phase9x_v53_alpha_sensitivity.pyDELIVERED 2026-04-27 11:45 HKTartifacts/phase9x_v53_alpha_sensitivity/{alpha_sensitivity.json, input_metrics.csv, alpha_scores.csv, alpha_sensitivity.md} (rank-only v5.3 committee sensitivity across existing Boltz-2, Vina n=20, tauRAMD n=20, and ADMET-AI axes. Score = mean_affinity_rank + alpha*mean_kinetic_rank + mean_admet_rank, lower better. adamantyl_acylsulfonamide_SO2Me_-Cl remains rank-1 for alpha 0.5-2.0; supports practical lead robustness without unit-mixing.)STRC h01 Phase 9x v5.3 Lead Committee Alpha Sensitivity 2026-04-272026-04-27
models/artifacts/phase8c_v5_3_admet/ (inline ADMET-AI runner via /opt/miniconda3/envs/admet-ai/bin/admet_predict)DELIVERED 2026-04-26 20:25 UTCmodels/artifacts/phase8c_v5_3_admet/{v5_3_admet_raw.csv, v5_3_admet_summary.{csv,json}, run.log} (ADMET-AI Lightning ensemble forward pass on 3 v5.3 SMILES from phase5p library. 10-endpoint drugbank-approved-percentile gate at 90.0. Result: 2/3 fully clean — adamantyl_-Cl and adamantyl_-CF3 (0 flags); affinity-rank-1 1-indanyl_-Cl has 1 borderline flag (CYP3A4_Veith 90.4 vs 90.0). Inline runner pattern, not a checked-in script.)STRC h01 Phase 8c v5.3 ADMET-AI Triage 2026-04-262026-04-26
scripts/phase5q_trpm4_dock_v53.shscaffold (next-session, conditional on lemma gate)models/docking_runs/6c_offtarget/TRPM4/poses_8g/{v5.3__aq3__*acylsulfonamide*.pdbqt} (Vina exh=16 dock of v5.3 top-3 onto TRPM4 8RD9 receptor PDBQT, pocket centre (152.46, 150.45, 134.72) Å from Phase 7I/8G mean dock centroid. ~10 min. Step 4 of v5.3 cross-target pipeline; only run if Phase 5q STRC σ ≥ 3×.)(lemma cross-target validation path)2026-04-26
scripts/phase5q_trpm4_taramd_v53.pyscaffold (next-session, conditional)artifacts/phase5q_trpm4_v53/{per_ligand/<lig>/.../result.json, ranking.{json,md}} (Phase 5m TRPM4 clone with v5.3 LIGANDS + LIB_CSV → v53_library.csv + OUT → phase5q_trpm4_v53. Cross-target τRAMD on v5.3 sulfonamide. ~3h Metal GPU. Final answer to “does sulfonamide chemistry break the within-target → cross-target lemma’s bound on this scaffold class?”.)(paper Figure 3 expansion)2026-04-26
phases/STRC h01 Phase 5e-v3 v3b-top50 Mutant Ensemble Re-Dock 2026-04-26 SKELETON.mdscaffold (in flight 2026-04-26, D-v3 at snap_013/20 ~70%)proof note shell with structure for: top-10 Vina v3 ranking, full ΔΔG mut-WT distribution, candidates with mut-tighter signal worth Phase 5e-v4 NAGL+soft-receptor follow-up. Numbers will be filled by next wakeup at 15:53 UTC.(will be canonical after D-v3 finishes)2026-04-26
autoresearch/phase5e_v2_rho_optimizer/{program.md, eval.py, history.jsonl, README.md}scaffold (Pilot Zero, no experiments yet 2026-04-26)(closed-loop autoresearch harness adapting karpathy/autoresearch pattern: agent edits phase5e_v2_mutant_redock.py to optimize Spearman ρ(Vina ΔG, −τRAMD median) on v5.2 shortlist; baseline ρ=−0.9, gate ρ≥+0.5 PASS-2, ρ≥+0.7 PASS-3 STOP. WALL_BUDGET_S=1800/experiment. Decision rules + ground-truth + bridge to NGAM all baked into program.md. First overnight run pending 2026-04-27.)Autoresearch Adaptation for STRC Computational Research2026-04-26

h03 — Mini-STRC Single-Vector AAV (S-tier) | h03 hub

ScriptStatusOutputBacksLast successful run
mini_strc_interface_preservation.pyactivemini_strc_interface_preservation.jsonSTRC Mini-STRC Truncation Interface Validation2026-04-21
cpg_depletion_mini_strc.pyactive (sibling)cpg_depletion_mini_strc.json, _v0.fasta, _max.fastaSTRC CpG Depletion Mini-STRC2026-04-21
cpg_depletion_ultra_mini_strc.pyactivecpg_depletion_ultra_mini_strc.json, _v0.fasta, _max.fastaSTRC Ultra-Mini CpG Depletion2026-04-21
strc_homodimer_interface_from_cif.pyactivestrc_homodimer_interface_from_cif.jsonSTRC Homodimer Interface From CIF2026-04-21
ultramini_homodimer_consensus.pyactiveultramini_homodimer_consensus.jsonSTRC Homodimer Interface From CIF (Ultra-Mini section)2026-04-21
ultra_mini_promoter_shortlist.pyactiveultra_mini_promoter_shortlist.jsonSTRC Ultra-Mini Promoter Shortlist · STRC h03 B8 Enhancer Bp Resolved 2026-04-242026-04-24 (B8 587→706 bp, post-split path cleanup)
ultramini_vector_cpg_audit.pyactiveultramini_vector_cpg_audit.jsonSTRC Ultra-Mini CpG Depletion (full-vector audit appendix) · STRC h03 B8 Enhancer Bp Resolved 2026-04-242026-04-24 (B8 587→706 bp, post-split path cleanup)

h04 — Strategy B mRNA-LNP Full-Length (B-tier) | h04 hub

ScriptStatusOutputBacksLast successful run
strc_mrna_strategy_b_pkpd.pyactive (post-split path fixed to ~/STRC/models)strc_mrna_strategy_b_pkpd.jsonSTRC mRNA-LNP Strategy B Full-Length (PK/PD core)2026-04-27
strategy_b_audiogram_rescue.pyactivestrategy_b_audiogram_rescue.jsonSTRC mRNA-LNP Strategy B Full-Length (audiogram appendix)2026-04-21
mrna_lnp_pkpd_integration.pyactive (Strategy A baseline)mrna_lnp_pkpd_integration.jsonSTRC mRNA-LNP PKPD Multi-Dose Schedule (Strategy A)2026-04-21
mrna_lnp_audiogram_rescue.pyactive (Strategy A baseline; post-split path fixed to ~/STRC/models)mrna_lnp_audiogram_rescue.jsonSTRC mRNA-LNP PKPD Multi-Dose Schedule (Strategy A audiogram)2026-04-27
mrna_stability_cochlear_results.json(no script — manual data)—STRC mRNA stability in cochlea (TODO phase-proof)2026-04-20

h02 — Piezoelectric TM Bioelectronic Amplifier (S-tier) | h02 hub

ScriptStatusOutputBacksLast successful run
piezo_voltage_budget.pyactivepiezo_voltage_budget_results.json, .pngSTRC Piezoelectric TM Bioelectronic Amplifier (Phase 1)2026-04-20
piezo_phase2_frequency_bundle.pyactivepiezo_phase2_results.json, .pngSTRC Piezoelectric TM Bioelectronic Amplifier (Phase 2)2026-04-20
piezo_phase3_delivery_feasibility.pyactivepiezo_phase3_delivery.json, .pngSTRC Piezo Delivery Feasibility OHC Targeting2026-04-20

h05 — Calcium Oscillation Acoustic Therapy (A-tier) | h05 hub

ScriptStatusOutputBacksLast successful run
ca_oscillation_rbm24_ode.pyactiveca_oscillation_rbm24_results.json, .pngSTRC Calcium Oscillation Acoustic Therapy (Phase 1 RBM24 path)2026-04-20
ca_oscillation_ac1_creb_pivot.pyactiveca_oscillation_ac1_creb_results.json, .pngSTRC AC1-CREB Alternative Hypothesis2026-04-20
ca_oscillation_phase2_sensitivity.pyactiveca_oscillation_phase2_sensitivity.json, .pngSTRC Calcium Oscillation Acoustic Therapy (Phase 2)2026-04-20
ca_oscillation_phase3_bifurcation.pyactiveca_oscillation_phase3_bifurcation.jsonSTRC Calcium Oscillation Acoustic Therapy (Phase 3)2026-04-21

h06 — Strategy A mRNA / RBM24 (B-tier, was A) | h06 hub

Shares mrna_lnp_pkpd_integration.py and mrna_lnp_audiogram_rescue.py with Strategy B (above).

ScriptStatusOutputBacksLast successful run
mrna_lnp_pkpd_hill_sensitivity.pyactive (post-split path fixed to ~/STRC/models)mrna_lnp_pkpd_hill_sensitivity.jsonSTRC h06 Hill Sensitivity Sweep 2026-04-232026-04-27

h07 — Prime Editing for STRC (C-tier) | h07 hub

ScriptStatusOutputBacksLast successful run
pe_phase1_pegrna_design.pyactivepe_phase1_pegrna_design.jsonPrime Editing for STRC (Phase 1 SpCas9-NGG)2026-04-21
pe_phase2_pam_expansion.pyactivepe_phase2_pam_expansion.jsonPrime Editing for STRC (Phase 2 PAM expansion)2026-04-21
pe_phase3_allele_discrimination.pyactivepe_phase3_allele_discrimination.jsonSTRC pe_phase3_allele_discrimination2026-04-21
pe_phase4_cas_offinder.pyactive (macOS Apple Silicon numpy fallback)pe_phase4_cas_offinder.jsonSTRC PE Phase4 STRCP1 Paralog Off-Target2026-04-22
pe_phase3_5_strcp1_aware.pyactivepe_phase3_5_strcp1_aware.jsonSTRC PE Phase 3_5 STRCP1-Aware Redesign2026-04-23

h08 — ASO Exon Skipping (C-tier) | h08 hub

ScriptStatusOutputBacksLast successful run
aso_phase1_design.pyactiveaso_phase1_design.json, aso_phase1_candidates.csvSTRC ASO Phase1 Splice-Switch Design2026-04-21
(ad-hoc fold check 2026-04-22)one-shot in conversation logaso_phase1_fold_check.jsonSTRC ASO Phase1 Fold Check2026-04-22 — needs lifting into a proper aso_phase1_fold_check.py if re-run
aso_phase2_strcp1_specificity.pyactive (pure-numpy, no external deps)aso_phase2_strcp1_specificity.jsonSTRC ASO Phase2 STRCP1 Paralog Cross-Hybridization2026-04-22
ohc_strcp1_expression_check.pyactive (stdlib + urllib only, queries GTEx v8)ohc_strcp1_expression_check.jsonSTRC STRCP1 GTEx Expression Check2026-04-22
mrna_lnp_pkpd_integration_v2_ohc_tropism.pyactive (v2: adds 1-3% tropism row + ER/UPR 5× ceiling; post-split path fixed to ~/STRC/models)mrna_lnp_pkpd_integration_v2_ohc_tropism.jsonSTRC mRNA-LNP PKPD v2 OHC Tropism2026-04-27

h15 — OTOA Paralog Cross-Rescue (D/C-tier) | h15 hub

ScriptStatusOutputBacksLast successful run
otoa_phase1_sequence_alignment.pyactive (frozen — hypothesis killed)otoa_phase1_sequence_alignment.jsonSTRC OTOA Paralog Cross-Rescue (Phase 1A)2026-04-20
otoa_phase1b_structure_alignment.pyactive (frozen — chimera killed by 13.8 Å RMSD)otoa_phase1b_structure_alignment.jsonSTRC OTOA Paralog Cross-Rescue (Phase 1B)2026-04-20

h09 — Synthetic Peptide Hydrogel HTC (A-tier) | h09 hub

ScriptStatusOutputBacksLast successful run
hydrogel_phase1_self_assembly.pyactivehydrogel_phase1_self_assembly.jsonSTRC Hydrogel HTC Phase 1 Self-Assembly (Phase 1)2026-04-23
af3_jobs_2026-04-23b_hydrogel_builder.pyactiveaf3_jobs_2026-04-23b_hydrogel/ (6 JSONs)STRC Hydrogel HTC Phase 1 Self-Assembly (Phase 2)2026-04-23
af3_jobs_2026-04-23b_hydrogel/analysis_summary.pyactiveaf3_jobs_2026-04-23b_hydrogel/analysis_summary.jsonSTRC Hydrogel HTC Phase 1 Self-Assembly (Phase 2 results)2026-04-23
af3_jobs_2026-04-23c_hydrogel_retool_builder.pyactiveaf3_jobs_2026-04-23c_hydrogel_retool/ (3 JSONs)STRC Hydrogel HTC Phase 1 Self-Assembly (Phase 3)2026-04-23
af3_jobs_2026-04-23c_hydrogel_retool/analysis_summary.pyactiveaf3_jobs_2026-04-23c_hydrogel_retool/analysis_summary.jsonSTRC Hydrogel HTC Phase 1 Self-Assembly (Phase 3 results)2026-04-23
af3_jobs_2026-04-23e_hydrogel_phase3b_builder.pyactiveaf3_jobs_2026-04-23e_hydrogel_phase3b/ (4 JSONs)STRC Hydrogel HTC Phase 1 Self-Assembly (Phase 3b)2026-04-23
af3_jobs_2026-04-23e_hydrogel_phase3b/analysis_summary.pyactiveaf3_jobs_2026-04-23e_hydrogel_phase3b/analysis_summary.jsonSTRC Hydrogel HTC Phase 1 Self-Assembly (Phase 3b results)2026-04-23
hydrogel_phase4a_cif_interface_forensics.pyactivehydrogel_phase4a_cif_interface_forensics.jsonSTRC Hydrogel Phase 4 Computational Campaign (4a)2026-04-23
af3_jobs_2026-04-23f_hydrogel_phase4b_builder.pyactiveaf3_jobs_2026-04-23f_hydrogel_phase4b/ (8 JSONs)STRC Hydrogel Phase 4 Computational Campaign (4b batch)2026-04-23
hydrogel_phase4c_sequence_liabilities.pyactivehydrogel_phase4c_sequence_liabilities.jsonSTRC Hydrogel Phase 4 Computational Campaign (4c)2026-04-23
hydrogel_phase4d_factin_bundling_model.pyactivehydrogel_phase4d_factin_bundling_model.jsonSTRC Hydrogel Phase 4 Computational Campaign (4d)2026-04-23
hydrogel_phase4e_cochlear_pkpd.pyactivehydrogel_phase4e_cochlear_pkpd.jsonSTRC Hydrogel Phase 4 Computational Campaign (4e)2026-04-23
hydrogel_phase4f_mhc_immunogenicity.pyactivehydrogel_phase4f_mhc_immunogenicity.jsonSTRC Hydrogel Phase 4 Computational Campaign (4f)2026-04-23
hydrogel_phase4g_spps_feasibility.pyactivehydrogel_phase4g_spps_feasibility.jsonSTRC Hydrogel Phase 4 Computational Campaign (4g)2026-04-23
hydrogel_phase4h_endogenous_strc_competition.pyactivehydrogel_phase4h_endogenous_strc_competition.jsonSTRC Hydrogel Phase 4 Computational Campaign (4h)2026-04-23
hydrogel_phase4e_v2_blend_scaffold.pyactivehydrogel_phase4e_v2_blend_scaffold.jsonSTRC h09 Phase 4e_v2 Blend Scaffold2026-04-23
hydrogel_phase4i_kd_sensitivity.pyactivehydrogel_phase4i_kd_sensitivity.jsonSTRC h09 Phase 4i Kd Sensitivity Sweep 2026-04-232026-04-23
hypotheses/h09-hydrogel/scripts/phase4b_af3_robustness_parser.pyactive (executed 2026-04-26)artifacts/phase4b_robustness/{aggregate.json, per_job.json, aggregate.tsv} (canonical robustness gate parser; takes either Anna’s-Archive-style result ZIPs from ~/STRC/models/af3_results/h09_phase4b/ OR direct AFS-page-scraped ipTM/pTM tables; computes per-axis median ipTM ± σ and applies the gate criterion median ≥0.50 AND σ <0.05; ablation-aware so noWH2 + triple-complex jobs go to a misc bucket. Used 2026-04-26 to deliver Phase 4b verdict: tmem145 median 0.60±0.037 PASS, actin 0.51±0.028 PASS, A→tentative-S triggered.)STRC h09 Phase 4b AF3 Robustness Gate 2026-04-262026-04-26
hypotheses/h09-hydrogel/scripts/phase4j_avidity_kd_model.pyactive (executed 2026-04-26)artifacts/phase4j_avidity_kd_2026-04-26.json (closed-form Mammen-Jencks-Karpen polyvalent avidity Kd model for RADA16-tail91 fibril × F-actin filament; pure-analytic substitute for wet-lab Phase 2c gate under no-wet-lab project rule. Inputs: Husson 2010 Tβ4 × F-actin floor 5–10 mM, Mammen 1998 rigid-scaffold C_eff range 50–500 mM, Karpen 1998 explicit C_eff formula. Sweeps Kd_mono × C_eff × N grid (4×4×5=80) and reports per-cell Kd_eff vs 50 µM gate. Conservative scenario FAIL by 1.6× (80 µM); nominal PASS by 1500× (31 nM); 47/80 grid PASS (59%). Triggers Phase 4k (AF3 fibril×F-actin patch) as gate-closer.)STRC h09 Phase 4j Avidity Kd Model 2026-04-262026-04-26
hypotheses/h09-hydrogel/scripts/phase4k_af3_fibril_actin_builder.pyactive (submitted 2026-04-27)~/STRC/models/af3_jobs_2026-04-27_h09_phase4k_fibril_actin/ (5 AF3 JSON jobs; 3 multi-copy construct + 2 covalent-tandem-WH2 forced-proximity proxy; tests if N>=4 simultaneous WH2 x actin contacts is geometrically achievable. Full 2026-04-27 result: geometric contacts appear only in tandem proxies; confidence-supported contact gate does not pass.)STRC h09 Phase 4k Fibril Actin Geometry 2026-04-272026-04-27
hypotheses/h09-hydrogel/scripts/phase4k_af3_contact_parser.pyactive (executed 2026-04-27)artifacts/phase4k_contact_parse_2026-04-27.json (standard-library parser for downloaded AFS ZIPs. Counts WH2 motif contacts against actin from top-model CIF coordinates, then separates raw geometric contacts from confidence-supported contacts using chain-pair ipTM >=0.20. Full result: any geometric pass=true; any confidence-supported pass=false; construct_x4 ipTM 0.37 / pTM 0.49 / 0 contacts; tandem x5 ipTM 0.72 but 0 confidence-supported WH2-actin contacts.)STRC h09 Phase 4k Fibril Actin Geometry 2026-04-272026-04-27
hypotheses/h09-hydrogel/scripts/phase4m_iptm_kd_calibration_builder.pyactive (submitted 2026-04-27)~/STRC/models/af3_jobs_2026-04-27_h09_phase4m_iptm_kd_calibration/ (6 AF3 JSON jobs; 5 Chereau 2005 ITC-measured WH2 × G-actin reference pairs (WAVE2, WIP, MIM, WASP, Tβ4) + 1 h09 tail91 N-term WH2 query. UniProt-retrieved sequences. Used for within-family ipTM-vs-log(Kd) regression to soft-floor h09 WH2 × F-actin Kd_mono. Caveat baked in: AF3 ipTM is NOT calibrated Kd predictor; comparative ratios only.)STRC h09 Phase 4m Kd Mono Soft Floor Result 2026-04-272026-04-27
hypotheses/h09-hydrogel/scripts/phase4m_iptm_kd_analysis.pyactive (executed 2026-04-27)artifacts/phase4m_calibration_2026-04-27.json (post-submission analysis populated from completed AFS ZIPs. Linear fit log(Kd) vs ipTM: R2=0.690; h09 ipTM=0.60 predicts Kd_G=1.48e-7 M and Tβ4-scaled Kd_F=1.48 mM. Pre-registered checks all PASS: R2>=0.5, h09 ipTM in [0.4,0.75], predicted Kd_F<5 mM. Re-run Phase 4j with Kd_mono=1.48 mM: C_eff=50 mM, N=3 gives Kd_eff=1.30 uM PASS.)STRC h09 Phase 4m Kd Mono Soft Floor Result 2026-04-272026-04-27
hypotheses/h09-hydrogel/scripts/phase4k_4m_4b_v2_combined_builder.pystaged (built 2026-04-26)~/STRC/models/af3_jobs_2026-04-27_h09_combined_13jobs.json (one-shot Upload-JSON payload combining all 13 tomorrow-batch jobs: 5×Phase 4k + 6×Phase 4m + 2×Phase 4b_v2 deferred. Single click upload at AFS quota refresh; ≤30 daily quota, ≤100-job upload limit, all jobs ≤2000 aa each.)STRC h09 Phase 4j Avidity Kd Model 2026-04-26n/a (staged)
hypotheses/h09-hydrogel/scripts/phase4n_avidity_montecarlo.pyactive (executed 2026-04-26)artifacts/phase4n_montecarlo_2026-04-26.json (Monte Carlo 100k samples + first-order conditional sensitivity over Phase 4j priors. Inputs: Kd_mono ~ LogU(1, 20) mM; C_eff ~ LogU(13.4, 500) mM; N ~ U{3,4,5,6}. Headline: P(PASS, ideal cooperativity) = 0.803 [95% CI 0.801, 0.806]; P(PASS, 30× Mammen entropic haircut) = 0.590 [95% CI 0.587, 0.593]. Sensitivity ranking: Kd_mono ΔP=0.51 > C_eff ΔP=0.45 > N ΔP=0.26 — reorders gate-tightening priority Phase 4m > Phase 4l > Phase 4k. Numpy/Accelerate; runs in ~3 s on M5 Max CPU.)STRC h09 Phase 4n Avidity Monte Carlo 2026-04-262026-04-26
hypotheses/h09-hydrogel/scripts/phase4p_boltz_wh2_control_builder.pyactive (executed 2026-04-27)models/boltz_jobs_2026-04-27_h09_wh2_controls/ (9 Boltz-2 YAML jobs: Chereau WH2 positives, Tbeta4 weak reference, h09 query, scrambled/alanine/poly-GS negatives; all against one G-actin monomer under matched protocol.)STRC h09 Phase 4p Boltz WH2 Orthogonal Controls 2026-04-272026-04-27
hypotheses/h09-hydrogel/scripts/phase4p_boltz_wh2_control_parser.pyactive (executed 2026-04-27)artifacts/phase4p_boltz_wh2_controls_2026-04-27.json (parses Boltz confidence JSONs from models/boltz_runs/h09_phase4p_wh2_controls/; result PASS-supportive: h09 ipTM=0.706, all negatives lower; WIP false-low and Tbeta4 false-high keep the result reviewer-support only, not ranking-moving.)STRC h09 Phase 4p Boltz WH2 Orthogonal Controls 2026-04-272026-04-27

h26 — Engineered Homodimer Avidity (B-tier) | h26 hub

ScriptStatusOutputBacksLast successful run
af3_jobs_2026-04-23d_engineered_homodimer_builder.pyactiveaf3_jobs_2026-04-23d_engineered_homodimer/ (5 JSONs)STRC Engineered Homodimer Avidity (Phase 1)2026-04-23
af3_jobs_2026-04-23d_engineered_homodimer_forensics.pyactivehypotheses/h26-engineered-homodimer/artifacts/phase1_af3_2026-04-23/af3_jobs_2026-04-23d_engineered_homodimer_analysis.jsonSTRC Engineered Homodimer Phase 1 Results2026-04-23
engineered_homodimer_phase1c_contact_cluster.pyactiveengineered_homodimer_phase1c_contact_cluster.jsonSTRC h26 Phase 1c Contact Re-Cluster 2026-04-232026-04-23

shared / cross-hypothesis

ScriptStatusOutputBacksLast successful run
ipsae_strc_reassess.shactiveartifacts/ipsae/*.txt (6 jobs × 3 outputs each)STRC ipSAE Cross-Complex Reassessment 2026-04-23 — h09 gate 3 narrowing + #26 Mech 3→22026-04-23
af3_jobs_2026-04-22_builder.pyactiveaf3_jobs_2026-04-22/ (4 JSONs + MANIFEST)STRC SpyCatcher Assembly Phase 1 Geometry, STRC TECTA Chimera Phase 1 Fold Check2026-04-22
af3_jobs_2026-04-22/analysis_summary.pyactiveaf3_jobs_2026-04-22/analysis_summary.jsonSTRC SpyCatcher Assembly Phase 1 Geometry (Phase 1a), STRC TECTA Chimera Phase 1 Fold Check2026-04-23
af3_jobs_2026-04-23_builder.pyactiveaf3_jobs_2026-04-23/ (2 JSONs + MANIFEST)STRC SpyCatcher Assembly Phase 1 Geometry (Phase 1b, aa 700 split)2026-04-23
af3_jobs_2026-04-23/analysis_summary.pyactiveaf3_jobs_2026-04-23/analysis_summary.jsonSTRC SpyCatcher Assembly Phase 1 Geometry (Phase 1b results)2026-04-23
strc_aav_lnp_stack_pkpd.pyactive (post-split path fixed to ~/STRC/models)strc_aav_lnp_stack_pkpd.jsonSTRC AAV-LNP Stack PKPD (h03+h04 joint)2026-04-27
ca_osc_maternal_allele_only.pyactiveca_osc_maternal_allele_only.jsonSTRC Ca Oscillation Maternal-Only PD (h05 Misha-specific)2026-04-23

ref — Misha-specific therapy integration

ScriptStatusOutputBacksLast successful run
misha_compound_het_stack_model.pyactivemisha_compound_het_stack_model.jsonMisha Compound-Het Therapy Stack Model2026-04-23

shared / uncategorized — Reference supporting models

ScriptStatusOutputBacksLast successful run
abr_transfer_model.pyactive (referenced from audiogram models)abr_transfer_results.jsonSTRC ABR Transfer Function Model2026-04-17
stereocilia_bundle_mechanics.pyactive (referenced from Piezo + Mini-STRC)bundle_mechanics_results.jsonSTRC Stereocilia Bundle Mechanics Model2026-04-17
therapeutic_window_model.pyactive (referenced from multiple)therapeutic_window_results.jsonAdult Treatment Window STRC2026-04-17
rescue_threshold_model.pyactive (combined therapeutic window + ABR)rescue_threshold_results.jsonSTRC Rescue Threshold2026-04-17
dual_vector_otof_calibration.pyactive (calibration anchor for AAV models)dual_vector_otof_results.jsonSTRC Dual-Vector vs Single-Vector Transduction2026-04-17
sonoporation_model.pyactive (sonogenetic delivery sub-model)(no JSON output found?)Sonogenetic STRC Computational Proof (paused C-tier)2026-04-17

Ad-hoc data extracts (no formal driver script)

Output JSONSourceBacks
af3_ultramini_results_2026-04-21.jsonmanual collation of AF3 server outputsSTRC AF3 Ultra-Mini Multimer Validation
strc_e1_conservation_nmd_motifs.jsonone-shot conservation extractSTRC E1 Conservation and NMD Motifs
strc_exon_protein_mapping.jsonone-shot mappingSTRC RBM24 Exon Mapping to Human Protein
strc_tmem145_interface_from_cif.jsonolder variant of strc_homodimer_interface_from_cif.py (predecessor; now superseded by mini_strc_interface_preservation.py for the TMEM145 zone)(legacy reference — superseded)
rbm24_mrna_dose_response_results.jsonolder Strategy A dose-response, retained as historicalSTRC mRNA Therapy Hypothesis
rbm24_sd03_splicing_analysis.jsonone-shot Sun et al. 2026 SD03 ingestionSTRC RBM24 Exon Splicing Quantification
pharmacochaperone_phase3b_virtual_screen.json (×2 entries — Phase 3B output collated)by Phase 3B scriptas Phase 3B above
aso_phase1_fold_check.jsonad-hoc 2026-04-22 (this conversation)STRC ASO Phase1 Fold Check

Outside the canonical models/ directory

ScriptLocationStatusNotes
rbm24_scan.py./ (root)active (older RBM24 motif scan)predecessor of ca_oscillation_rbm24_ode.py; retained for replication
rbm24_scan_v2.py./ (root)active (refactored RBM24 motif scan)sibling of rbm24_scan.py
rbm24_scan 2.py./ (root)duplicate (iCloud sync conflict)identical to rbm24_scan.py; flagged for cleanup, do not auto-delete
rbm24_scan_v2 2.py./ (root)duplicate (iCloud sync conflict)identical to rbm24_scan_v2.py; flagged for cleanup
pharmacochaperone_phase4f_interface_rescue.pyalso at ~/Desktop/strc-jobs-2026-04-22/bundle copythe canonical version lives in models/; bundle copy is for taildrop transfer
pe_phase4_cas_offinder.py тоalso at ~/Desktop/strc-jobs-2026-04-22/bundle copyas above

Audit findings (2026-04-22)

Scaffolds that never ran (kill if not advancing in 30 days):

  • pharmacochaperone_phase4d_k1141a_decoy.py — explicitly skipped per Phase 4c interpretation; safe to delete after Phase 4f closes if 4f passes.
  • pharmacochaperone_phase5_md.py — Phase 5 GROMACS MD; deferred until Phase 4f result lands. Keep as scaffold reservation; flesh out once 4f closes.

Duplicates (iCloud sync conflicts):

  • rbm24_scan 2.py, rbm24_scan_v2 2.py — same content as their no-suffix siblings. Keep flagged here; remove manually after a diff confirms identity.

Possibly orphaned outputs (no clear note backref or older than 4 days without update):

  • strc_tmem145_interface_from_cif.json — predecessor of mini-STRC interface preservation; data is interesting but not currently referenced in any active proof. Decide: re-link to a note or move to _archive/.

Things missing that probably should exist:

Things that should be moved to a proper inventory:

  • This note is the inventory. Future scripts go here.

Connections

  • [part-of] STRC Research Portal
  • STRC E1659A Computational Tool Audit — that one tracks 143 third-party prediction tools; this one tracks our hand-written drivers
  • STRC Hypothesis Ranking — every script ultimately backs a row in the ranking
  • [applies] Misha — every active script targets Misha’s variant or paternal deletion

Graph View

Backlinks