{
  "schema": "dia-health-one.public-confidence-status.v1",
  "updated": "2026-11-04",
  "program_stage": "hypothesis",
  "working_drug_discovered": false,
  "measured_dia_health_one_hit": false,
  "primary_candidate": {
    "id": "MC-Q1",
    "evidence_level": "E2",
    "status": "defined and computationally stress-tested; not synthesized or measured",
    "mechanism_label": "contact-site polarity/electronic/solvation hypothesis",
    "simple_steric_block_claim_supported": false
  },
  "published_reference": {
    "nnc2215_glucose_responsive": true,
    "nnc2215_viable_therapeutic_candidate": false,
    "nnc2215_glucose_kd_mM": 1.91,
    "nnc2215_pag_kd_mM": 0.17,
    "pag_preference_fold_point_estimate": 11.235294117647058,
    "clinically_relevant_pag_effect_reported": true
  },
  "computational_evidence": {
    "contact_site_pose_grid_size": 13824,
    "contact_site_placements_below_4A": 5376,
    "distal_a_placements_below_4A": 0,
    "distal_b_placements_below_4A": 0,
    "mcq1_contact_methoxy_clash_free_rotamers": 72,
    "mcq1d_distal_a_clash_free_rotamers": 72,
    "distal_b_clash_free_rotamers": 52,
    "calibrated_affinity_prediction_available": false
  },
  "minimum_physical_experiment": [
    "MC-P0",
    "MC-Q1",
    "MC-Q1D",
    "MC-P3"
  ],
  "first_expansion_control": "MC-P1",
  "direct_binding_advance_gate": {
    "minimum_kd_pag_over_kd_glucose": 5,
    "lower_95_percent_bound_must_exceed": 1,
    "maximum_glucose_affinity_loss_vs_parent_fold": 5,
    "orthogonal_method_required": true,
    "must_outperform_positional_control": true
  },
  "aws_execution": {
    "current_gate": "AWS-1 acquisition defined; awaiting checksum-verified download and AWS access",
    "candidate_screen_authorized": false,
    "boltz_host_guest_affinity_authorized": false,
    "hill_curve_from_concentration_labelled_structure_predictions_authorized": false,
    "aws_credits_spent_usd": 0,
    "initial_download_size_display": "41.6 MB plus 1.8 kB README",
    "source_dataset_doi": "10.5281/zenodo.19664426",
    "source_dataset_manifest": "../GLUHUT_AWS1_DATASET_MANIFEST.md",
    "next_action": "download and checksum-verify README.txt and WHAM_PMF.zip, then reproduce glucose US-1"
  },
  "next_confidence_changes": [
    "reproduce public GluHUT PMF analysis",
    "validate exact chemistry and force field",
    "calibrate a source-matched parent glucose-versus-PaG calculation",
    "obtain provider acceptance and synthesis quotation",
    "measure authenticated free-binder glucose and PaG binding"
  ]
}