{
  "version": 3,
  "created_at": "2026-07-09T14:40:27.997Z",
  "task_summary": "Design and visualize EoE pMHC tolerance therapeutics targeting wheat, dairy, and soy",
  "agents": [],
  "phases": [
    {
      "name": "Plan",
      "delegations": [
        {
          "steps": [
            {
              "title": "Assemble food-epitope core design table",
              "description": "For dairy/wheat/soy, select the top presentable 15-mer cores from the existing patient_epitope_panel.csv plus the tetramer-validated dairy anchor β-casein aa59–78/DRB1*07:01 (Dilollo/Spergel/Hill 2025). Fetch UniProt sequences for β-casein (P02666), α-gliadin, soy β-conglycinin and glycinin via the pipeline helper. Map each core to its minimal 9-mer register and restricting allele. Save eoe_pmhc_therapeutic_cores.csv with food, protein, UniProt, core, register, allele, IC50-prior, and validation-status columns."
            },
            {
              "title": "Design the three pMHC-II construct formats per food",
              "description": "Engineer, per food core, three backbones: (1) tolerogenic soluble single-chain pMHC-II (peptide–GS linker–HLA-DRβ1–linker–HLA-DRα1, no costimulation domain); (2) Navacim-style pMHC-II monomer for multivalent nanoparticle display (add ferritin/His-tag fusion handle); (3) depleting pMHC-II tetramer unit (biotinylation BirA-AviTag + streptavidin logic). Emit full amino-acid sequences with annotated segments. Save eoe_pmhc_constructs.fasta and a construct spec CSV."
            },
            {
              "title": "Build pMHC-II:peptide structural models (groove threading)",
              "description": "Fetch a real HLA-DR class-II template PDB (e.g. 1DLH / DR-peptide complex), thread each food core into the groove by mutating the bound peptide to the food 9-mer register, and relieve clashes. Produce one pMHC-II:peptide complex PDB per food (dairy_pmhc.pdb, wheat_pmhc.pdb, soy_pmhc.pdb) for the interactive 3D viewer, with the food peptide as a distinct chain."
            },
            {
              "title": "GPU co-fold / validate the flagship single-chain construct",
              "description": "On Modal GPU, co-fold the tolerogenic single-chain pMHC-II construct for the flagship dairy β-casein epitope (and wheat+soy if time) with a co-folding model (Chai-1 or ESMFold2) to confirm the designed backbone folds with the peptide seated in the groove. Report pLDDT/pTM and peptide-in-groove geometry. Save the predicted complex PDB(s) and a foldback_metrics table."
            },
            {
              "title": "Render the pMHC strategy figure",
              "description": "Using figure-style, produce a publication-grade multi-panel figure: (A) the 3-modality × 3-food strategy matrix schematic; (B) per-food epitope load / core selection; (C) construct architecture cartoons (single-chain, nanoparticle, tetramer); (D) structural groove panels showing each food peptide seated in HLA-DR. Save eoe_pmhc_strategy_figure.png."
            },
            {
              "title": "Write design report and spec sheets",
              "description": "Compile eoe_pmhc_therapeutic_report.md: rationale, per-food per-modality spec sheets, the tetramer-validated dairy anchor, and an explicit presentation≠pathology / prior-art (Hill–Spergel patent) guardrail section stating all binding is computational prior. Bundle FASTA, CSVs, PDBs, and figure. Save the report and a tar bundle."
            }
          ]
        }
      ],
      "id": "phase-0"
    }
  ],
  "feasibility": {
    "rationale": "Builds directly on existing project artifacts (epitope panel, food-trigger dx design, pMHC review) and the tetramer-validated dairy epitope. Epitope cores are in hand; construct design is sequence engineering on known HLA-II chains; structural models via groove threading + GPU co-folding on the available Modal target. Main honesty constraint: all binding is computational prior and presentation ≠ pathology (esp. wheat).",
    "confidence": "high"
  }
}