{
  "title": "Lp(a): from a blocked architecture to a computational candidate program",
  "recordType": "Public case summary of recorded computational work",
  "reviewDate": "2026-09-23",
  "scientificObjective": "Investigate a covalent intervention hypothesis for Lp(a).",
  "startingQuestion": "Could a second binding contact support the intended molecular design?",
  "comparison": "A bivalent architecture, with two recognition elements, was compared with a simpler monovalent covalent strategy. This was a within-program computational comparison, not a comparison with a competing platform.",
  "steps": [
    {
      "question": "Was the bivalent architecture actually beyond reach?",
      "recordedFinding": "The initial distance estimate used domain centers. Reassessment used the relevant pocket-to-attachment geometry.",
      "decision": "Reopen a geometrically feasible design branch for further investigation.",
      "evidenceType": "Static structural-model analysis"
    },
    {
      "question": "Did the more complex architecture add enough to the modeled objective?",
      "recordedFinding": "Kinetic and regimen modeling supported continuing the simpler monovalent covalent strategy.",
      "decision": "Keep the simpler design as the main computational strategy and retain the bivalent architecture as an option.",
      "evidenceType": "Conditional kinetic and regimen comparison"
    },
    {
      "question": "What was produced?",
      "recordedFinding": "A computational covalent candidate program with reasoned alternatives and a physical validation plan.",
      "decision": "Advance to the relevant synthesis, engagement and functional tests.",
      "evidenceType": "Computational design and research planning"
    }
  ],
  "meaning": "A structural correction changed which designs remained plausible. A second comparison changed which design was worth carrying forward. The useful outcome was a revisable candidate program, rather than a single score.",
  "validationBoundary": "Synthesis, binding, biological activity and therapeutic benefit are not established by this record. The modeled comparison depends on its structural, kinetic and exposure assumptions.",
  "recordBoundary": "This is a concise case-level account of the research. It is not a raw experimental dataset or a reproducibility package.",
  "programRoute": "/programs/lpa/"
}