Open Discovery Challenge #1 Malaria - submission intake and leaderboard

Scoring runs on a separate GPU worker, never in this service: docking takes minutes,
the tunnel cuts at ~125s, and an in-process boltz call already wedged an API once.
Submissions queue here and results are posted back.

Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>

.gitignore

@@ -0,0 +1,2 @@
+data/ledger.jsonl
+__pycache__/

Dockerfile

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+# HF Spaces runs the container as a non-root user; write only under paths we own.
+FROM python:3.11-slim
+RUN useradd -m -u 1000 user
+WORKDIR /app
+COPY requirements.txt .
+RUN pip install --no-cache-dir -r requirements.txt
+COPY . .
+RUN mkdir -p /app/data && chown -R user:user /app
+USER user
+ENV ODC_LEDGER=/app/data/ledger.jsonl
+EXPOSE 7860
+CMD ["uvicorn", "app:app", "--host", "0.0.0.0", "--port", "7860"]

README.md

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+---
+title: Open Discovery Challenge
+emoji: 🧬
+colorFrom: green
+colorTo: blue
+sdk: docker
+app_port: 7860
+pinned: false
+---
+
+# Open Discovery Challenge #1 — Malaria
+
+AI가 제안한 저분자 후보를 공개된 기준으로 자동 채점하는 개방형 신약 발굴 대회.
+
+- **표적** PfDHODH (*Plasmodium falciparum* dihydroorotate dehydrogenase)
+- **역표적** human DHODH — 기생충 효소만 막고 사람 것은 피해야 함
+
+점수는 **계산 기반 후보 평가**이며, 실제 효능·안전성이나 승인약과의 우열을 뜻하지 않습니다.

app.py

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+# -*- coding: utf-8 -*-
+"""Open Discovery Challenge - submission intake and leaderboard.
+
+Deliberately thin. Nothing here computes a score.
+
+Scoring needs docking, docking needs a GPU, and a docking call takes minutes: the tunnel
+in front of this service cuts a request at ~125 s, and boltz spawns grandchildren that
+hold the stdout pipe open so a subprocess call never returns and wedges the whole worker.
+That combination already took the PharmaOS API down once. So submissions land in a ledger
+here, a worker on the GPU box picks them up, and results come back the same way. One
+entrant can never block the service.
+
+Endpoints
+    GET  /                  leaderboard page
+    POST /api/submit        accept a structure, run the gates, queue it
+    GET  /api/leaderboard   ranked table, structures masked
+    GET  /api/queue         how much work is outstanding
+    GET  /api/pending       worker: claim unscored entries
+    POST /api/result        worker: post a score back
+"""
+import hashlib
+import json
+import os
+import time
+import uuid
+
+from fastapi import FastAPI, HTTPException, Request
+from fastapi.responses import FileResponse, JSONResponse
+from pydantic import BaseModel
+
+import gates
+
+HERE = os.path.dirname(os.path.abspath(__file__))
+LEDGER = os.environ.get("ODC_LEDGER", os.path.join(HERE, "data", "ledger.jsonl"))
+ANCHORS = os.path.join(HERE, "data", "anchor_scores.json")
+# Only the worker may post scores. Without this anyone could write their own.
+WORKER_KEY = os.environ.get("ODC_WORKER_KEY", "")
+# Masked identifiers must not be reversible from the public table.
+SALT = os.environ.get("ODC_SALT", "odc-season1")
+
+SEASON = {"name": "Open Discovery Challenge", "number": 1, "topic": "Malaria",
+          "target": "PfDHODH", "counter_target": "human DHODH",
+          "weights": {"약효": 30, "결합": 20, "선택성": 20, "ADMET": 15, "신규성": 10, "합성": 5}}
+
+app = FastAPI(title="Open Discovery Challenge")
+os.makedirs(os.path.dirname(LEDGER), exist_ok=True)
+
+
+class Submission(BaseModel):
+    structure: str            # SMILES or InChI
+    display_name: str         # name, affiliation or handle - entrant's choice
+    model_name: str = ""      # which model proposed it; free text, blank allowed
+    rationale: str = ""       # optional design note
+
+
+def _read():
+    if not os.path.exists(LEDGER):
+        return []
+    out = []
+    with open(LEDGER, encoding="utf-8") as f:
+        for line in f:
+            line = line.strip()
+            if line:
+                out.append(json.loads(line))
+    return out
+
+
+def _append(rec):
+    with open(LEDGER, "a", encoding="utf-8") as f:
+        f.write(json.dumps(rec, ensure_ascii=False) + "\n")
+
+
+def _latest():
+    """Last write per submission id wins, so a worker can post a score by appending."""
+    by_id = {}
+    for r in _read():
+        by_id[r["id"]] = {**by_id.get(r["id"], {}), **r}
+    return list(by_id.values())
+
+
+def public_id(inchikey):
+    """A stable public handle that cannot be walked back to the structure.
+
+    The skeleton block of an InChIKey is a hash of connectivity, so it is safe to show
+    and still lets anyone check two entries are the same compound. The full key and the
+    SMILES stay in the ledger."""
+    h = hashlib.sha256((SALT + inchikey).encode()).hexdigest()[:6].upper()
+    return "ODC-%s" % h
+
+
+def mask(rec):
+    """What the public table is allowed to see: enough to verify and compare, never
+    enough to reconstruct. Entrants keep their chemistry until they choose otherwise."""
+    return {
+        "candidate_id": rec.get("candidate_id"),
+        "skeleton": (rec.get("inchikey") or "")[:14],
+        "display_name": rec.get("display_name"),
+        "model_name": rec.get("model_name"),
+        "mw_band": rec.get("mw_band"),
+        "status": rec.get("status"),
+        "total": rec.get("total"),
+        "axes": rec.get("axes_points"),
+        "tier": rec.get("tier", 1),
+        "relegate_reason": rec.get("relegate_reason") or [],
+        "submitted_at": rec.get("submitted_at"),
+    }
+
+
+def band(x, step=50):
+    if x is None:
+        return None
+    lo = int(x // step) * step
+    return "%d-%d" % (lo, lo + step)
+
+
+@app.get("/")
+def index():
+    return FileResponse(os.path.join(HERE, "index.html"))
+
+
+@app.get("/api/season")
+def season():
+    return SEASON
+
+
+@app.post("/api/submit")
+def submit(s: Submission):
+    if not s.display_name.strip():
+        raise HTTPException(400, "표시 ID를 입력하세요")
+    # Season 1's target is not a covalent-mechanism enzyme, so that rule is off here.
+    v = gates.check(s.structure, covalent_rule=False)
+    if not v["admitted"]:
+        return JSONResponse({"accepted": False, "reasons": v["reject"]}, status_code=422)
+
+    existing = {r.get("inchikey") for r in _latest()}
+    if v["inchikey"] in existing:
+        return JSONResponse(
+            {"accepted": False,
+             "reasons": ["이미 제출된 구조입니다 (%s)" % public_id(v["inchikey"])]},
+            status_code=409)
+
+    rec = {
+        "id": uuid.uuid4().hex,
+        "candidate_id": public_id(v["inchikey"]),
+        "smiles": v["smiles"], "inchikey": v["inchikey"],
+        "mw": v["mw"], "mw_band": band(v["mw"]),
+        "display_name": s.display_name.strip()[:60],
+        "model_name": s.model_name.strip()[:80],
+        "rationale": s.rationale.strip()[:2000],
+        "status": "queued", "submitted_at": int(time.time()),
+    }
+    _append(rec)
+    ahead = sum(1 for r in _latest() if r.get("status") == "queued")
+    return {"accepted": True, "candidate_id": rec["candidate_id"],
+            "queue_position": ahead,
+            "note": "채점은 GPU 작업으로 처리되며 완료까지 몇 분 걸립니다."}
+
+
+@app.get("/api/leaderboard")
+def leaderboard():
+    rows = [mask(r) for r in _latest() if r.get("status") == "scored"]
+    anchors = []
+    if os.path.exists(ANCHORS):
+        for a in json.load(open(ANCHORS, encoding="utf-8")):
+            if not a.get("admitted"):
+                continue
+            anchors.append({"candidate_id": a["label"], "is_anchor": True,
+                            "display_name": "기준물질", "model_name": "",
+                            "total": a["total"], "tier": a.get("tier", 1),
+                            "axes": {k: v["points"] for k, v in a["axes"].items()},
+                            "note": a.get("note", "")})
+    merged = rows + anchors
+    merged.sort(key=lambda e: (e.get("tier", 1), -(e.get("total") or -1)))
+    n = 0
+    for e in merged:
+        if e.get("is_anchor") or e.get("tier", 1) != 1:
+            e["rank"] = None            # anchors mark the ladder; they do not climb it
+        else:
+            n += 1
+            e["rank"] = n
+    return {"season": SEASON, "entries": merged,
+            "counts": {"scored": len(rows), "anchors": len(anchors)}}
+
+
+@app.get("/api/queue")
+def queue():
+    rs = _latest()
+    return {"queued": sum(1 for r in rs if r.get("status") == "queued"),
+            "scoring": sum(1 for r in rs if r.get("status") == "scoring"),
+            "scored": sum(1 for r in rs if r.get("status") == "scored")}
+
+
+def _auth(request: Request):
+    if not WORKER_KEY or request.headers.get("X-Worker-Key") != WORKER_KEY:
+        raise HTTPException(401, "worker key required")
+
+
+@app.get("/api/pending")
+def pending(request: Request, limit: int = 5):
+    _auth(request)
+    out = [r for r in _latest() if r.get("status") == "queued"][:limit]
+    for r in out:
+        _append({"id": r["id"], "status": "scoring"})
+    return {"items": [{"id": r["id"], "smiles": r["smiles"],
+                       "candidate_id": r["candidate_id"]} for r in out]}
+
+
+@app.post("/api/result")
+async def result(request: Request):
+    _auth(request)
+    body = await request.json()
+    if "id" not in body:
+        raise HTTPException(400, "id required")
+    _append({"id": body["id"], "status": "scored",
+             "total": body.get("total"), "axes_points": body.get("axes_points"),
+             "tier": body.get("tier", 1), "relegate_reason": body.get("relegate_reason"),
+             "scored_at": int(time.time()), "run": body.get("run")})
+    return {"ok": True}

data/anchor_scores.json

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+[
+  {
+    "admitted": true,
+    "gate": {
+      "admitted": true,
+      "reject": [],
+      "relegate": [],
+      "notes": [],
+      "smiles": "Cc1cc(Nc2ccc(S(F)(F)(F)(F)F)cc2)n2nc(C(C)(F)F)nc2n1",
+      "inchikey": "OIZSVTOIBNSVOS-UHFFFAOYSA-N",
+      "mw": 415.34,
+      "heavy_atoms": 27
+    },
+    "relegated": false,
+    "relegate_reason": [],
+    "axes": {
+      "activity": {
+        "points": 14.45,
+        "detail": {
+          "pAct_q10": 5.467,
+          "fraction": 0.482
+        }
+      },
+      "binding": {
+        "points": 15.12,
+        "detail": {
+          "pIC50": 7.27,
+          "LE": 0.369,
+          "potency_term": 0.756,
+          "efficiency_cap": 1.0
+        }
+      },
+      "selectivity": {
+        "points": 12.59,
+        "detail": {
+          "fold": 46.3,
+          "selectivity_term": 0.833,
+          "target_engagement": 0.756
+        }
+      },
+      "admet": {
+        "points": 5.89,
+        "detail": {
+          "geometric_mean": 0.519,
+          "per_endpoint": {
+            "solubility-aqsoldb": 0.405,
+            "caco2-wang": 0.763,
+            "hia-hou": 1.0,
+            "bioavailability-ma": 1.0,
+            "pgp-broccatelli": 1.0,
+            "cyp2c9-veith": 0.349,
+            "cyp3a4-substrate-carbonmangels": 0.638,
+            "ld50-zhu": 0.66,
+            "herg": 0.116,
+            "dili": 0.05
+          }
+        }
+      },
+      "novelty": {
+        "points": 0.0,
+        "detail": {
+          "max_tanimoto": 1.0,
+          "novelty": 0.0
+        }
+      },
+      "synthesis": {
+        "points": 2.84,
+        "detail": {
+          "sa_score": 3.37
+        }
+      }
+    },
+    "total": 50.88,
+    "tier": 1,
+    "label": "DSM265",
+    "is_anchor": true,
+    "note": "임상후보 (양성 앵커)",
+    "rank": null
+  },
+  {
+    "admitted": true,
+    "gate": {
+      "admitted": true,
+      "reject": [],
+      "relegate": [],
+      "notes": [],
+      "smiles": "Cc1c(-c2ccc(-c3ccccc3F)cc2)nc2ccc(F)cc2c1C(=O)O",
+      "inchikey": "PHEZJEYUWHETKO-UHFFFAOYSA-N",
+      "mw": 375.37,
+      "heavy_atoms": 28
+    },
+    "relegated": false,
+    "relegate_reason": [],
+    "axes": {
+      "activity": {
+        "points": 2.58,
+        "detail": {
+          "pAct_q10": 4.755,
+          "fraction": 0.086
+        }
+      },
+      "binding": {
+        "points": 0.0,
+        "detail": {
+          "reason": "도킹 없음"
+        }
+      },
+      "selectivity": {
+        "points": 0.0,
+        "detail": {
+          "reason": "쌍 측정 없음"
+        }
+      },
+      "admet": {
+        "points": 0.47,
+        "detail": {
+          "geometric_mean": 0.363,
+          "per_endpoint": {
+            "solubility-aqsoldb": 0.05,
+            "caco2-wang": 0.714,
+            "hia-hou": 1.0,
+            "bioavailability-ma": 1.0,
+            "pgp-broccatelli": 0.766,
+            "cyp2c9-veith": 0.696,
+            "cyp3a4-substrate-carbonmangels": 0.88,
+            "ld50-zhu": 0.271,
+            "herg": 0.115,
+            "dili": 0.05
+          }
+        }
+      },
+      "novelty": {
+        "points": 0.56,
+        "detail": {
+          "max_tanimoto": 0.348,
+          "novelty": 0.652
+        }
+      },
+      "synthesis": {
+        "points": 0.43,
+        "detail": {
+          "sa_score": 2.06
+        }
+      }
+    },
+    "total": 4.04,
+    "tier": 1,
+    "label": "Brequinar",
+    "is_anchor": false,
+    "note": "사람 DHODH 억제제 (선택성 반례)",
+    "rank": 1
+  },
+  {
+    "admitted": true,
+    "gate": {
+      "admitted": true,
+      "reject": [],
+      "relegate": [],
+      "notes": [],
+      "smiles": "C/C(O)=C(\\C#N)C(=O)Nc1ccc(C(F)(F)F)cc1",
+      "inchikey": "UTNUDOFZCWSZMS-YFHOEESVSA-N",
+      "mw": 270.21,
+      "heavy_atoms": 19
+    },
+    "relegated": false,
+    "relegate_reason": [],
+    "axes": {
+      "activity": {
+        "points": 1.66,
+        "detail": {
+          "pAct_q10": 4.362,
+          "fraction": 0.055
+        }
+      },
+      "binding": {
+        "points": 0.0,
+        "detail": {
+          "reason": "도킹 없음"
+        }
+      },
+      "selectivity": {
+        "points": 0.0,
+        "detail": {
+          "reason": "쌍 측정 없음"
+        }
+      },
+      "admet": {
+        "points": 0.51,
+        "detail": {
+          "geometric_mean": 0.614,
+          "per_endpoint": {
+            "solubility-aqsoldb": 0.575,
+            "caco2-wang": 0.851,
+            "hia-hou": 1.0,
+            "bioavailability-ma": 1.0,
+            "pgp-broccatelli": 1.0,
+            "cyp2c9-veith": 0.568,
+            "cyp3a4-substrate-carbonmangels": 0.21,
+            "ld50-zhu": 0.459,
+            "herg": 1.0,
+            "dili": 0.11
+          }
+        }
+      },
+      "novelty": {
+        "points": 0.35,
+        "detail": {
+          "max_tanimoto": 0.357,
+          "novelty": 0.643
+        }
+      },
+      "synthesis": {
+        "points": 0.28,
+        "detail": {
+          "sa_score": 2.27
+        }
+      }
+    },
+    "total": 2.79,
+    "tier": 1,
+    "label": "Teriflunomide",
+    "is_anchor": false,
+    "note": "사람 DHODH 억제제 (선택성 반례)",
+    "rank": 2
+  },
+  {
+    "admitted": true,
+    "gate": {
+      "admitted": true,
+      "reject": [],
+      "relegate": [],
+      "notes": [],
+      "smiles": "CC(C)Cc1ccc(C(C)C(=O)O)cc1",
+      "inchikey": "HEFNNWSXXWATRW-UHFFFAOYSA-N",
+      "mw": 206.28,
+      "heavy_atoms": 15
+    },
+    "relegated": false,
+    "relegate_reason": [],
+    "axes": {
+      "activity": {
+        "points": 1.04,
+        "detail": {
+          "pAct_q10": 4.174,
+          "fraction": 0.035
+        }
+      },
+      "binding": {
+        "points": 0.06,
+        "detail": {
+          "pIC50": 3.57,
+          "LE": 0.326,
+          "potency_term": 0.003,
+          "efficiency_cap": 1.0
+        }
+      },
+      "selectivity": {
+        "points": 0.0,
+        "detail": {
+          "fold": 0.3,
+          "selectivity_term": 0.0,
+          "target_engagement": 0.0
+        }
+      },
+      "admet": {
+        "points": 0.38,
+        "detail": {
+          "geometric_mean": 0.74,
+          "per_endpoint": {
+            "solubility-aqsoldb": 0.677,
+            "caco2-wang": 1.0,
+            "hia-hou": 1.0,
+            "bioavailability-ma": 1.0,
+            "pgp-broccatelli": 1.0,
+            "cyp2c9-veith": 1.0,
+            "cyp3a4-substrate-carbonmangels": 1.0,
+            "ld50-zhu": 0.212,
+            "herg": 1.0,
+            "dili": 0.528
+          }
+        }
+      },
+      "novelty": {
+        "points": 0.21,
+        "detail": {
+          "max_tanimoto": 0.386,
+          "novelty": 0.614
+        }
+      },
+      "synthesis": {
+        "points": 0.17,
+        "detail": {
+          "sa_score": 2.19
+        }
+      }
+    },
+    "total": 1.86,
+    "tier": 1,
+    "label": "Ibuprofen",
+    "is_anchor": true,
+    "note": "음성대조",
+    "rank": null
+  },
+  {
+    "admitted": true,
+    "gate": {
+      "admitted": true,
+      "reject": [],
+      "relegate": [],
+      "notes": [],
+      "smiles": "Cn1c(=O)c2c(ncn2C)n(C)c1=O",
+      "inchikey": "RYYVLZVUVIJVGH-UHFFFAOYSA-N",
+      "mw": 194.19,
+      "heavy_atoms": 14
+    },
+    "relegated": false,
+    "relegate_reason": [],
+    "axes": {
+      "activity": {
+        "points": 1.1,
+        "detail": {
+          "pAct_q10": 4.197,
+          "fraction": 0.037
+        }
+      },
+      "binding": {
+        "points": 0.06,
+        "detail": {
+          "pIC50": 3.62,
+          "LE": 0.354,
+          "potency_term": 0.003,
+          "efficiency_cap": 1.0
+        }
+      },
+      "selectivity": {
+        "points": 0.0,
+        "detail": {
+          "fold": 1.3,
+          "selectivity_term": 0.058,
+          "target_engagement": 0.0
+        }
+      },
+      "admet": {
+        "points": 0.27,
+        "detail": {
+          "geometric_mean": 0.496,
+          "per_endpoint": {
+            "solubility-aqsoldb": 1.0,
+            "caco2-wang": 1.0,
+            "hia-hou": 1.0,
+            "bioavailability-ma": 1.0,
+            "pgp-broccatelli": 1.0,
+            "cyp2c9-veith": 1.0,
+            "cyp3a4-substrate-carbonmangels": 0.05,
+            "ld50-zhu": 0.096,
+            "herg": 0.1,
+            "dili": 0.58
+          }
+        }
+      },
+      "novelty": {
+        "points": 0.23,
+        "detail": {
+          "max_tanimoto": 0.367,
+          "novelty": 0.633
+        }
+      },
+      "synthesis": {
+        "points": 0.18,
+        "detail": {
+          "sa_score": 2.3
+        }
+      }
+    },
+    "total": 1.84,
+    "tier": 1,
+    "label": "Caffeine",
+    "is_anchor": true,
+    "note": "음성대조",
+    "rank": null
+  }
+]

gates.py

@@ -0,0 +1,138 @@
+# -*- coding: utf-8 -*-
+"""Season 1 admission gates.
+
+Gates decide eligibility, never quality. Anything that reflects how good a molecule is
+belongs in the continuous score; a gate only answers "is this a valid Season 1 entry".
+Failing a gate does not put a submission at the bottom of the table - it means the entry
+is returned, because a covalent warhead in a non-covalent season is not a bad candidate,
+it is the wrong kind of candidate.
+
+The one exception is ADMET, and it is deliberate: a candidate that fails a toxicity gate
+is still scored in full and still shown, but sorts below every clean entry no matter how
+high that score is. A molecule that binds beautifully and is mutagenic is not a lead.
+
+Every threshold here was checked against a panel of approved drugs first. A gate that
+rejects an approved drug is a broken gate, and two of the obvious candidates - hERG and
+DILI - were thrown out for exactly that reason: our own ADMET model scores ensitrelvir
+at hERG 0.978 and DILI 0.995, and caffeine at hERG 0.885. See data/anchors.json.
+"""
+from rdkit import Chem, RDLogger
+from rdkit.Chem import Descriptors
+from rdkit.Chem.FilterCatalog import FilterCatalog, FilterCatalogParams
+
+RDLogger.DisableLog("rdApp.*")
+
+_p = FilterCatalogParams()
+_p.AddCatalog(FilterCatalogParams.FilterCatalogs.PAINS)
+_PAINS = FilterCatalog(_p)
+
+MW_MAX = 550.0          # ensitrelvir is 531.9; a 500 cap would disqualify the reference drug
+HEAVY_MAX = 45
+AMES_MAX = 0.7          # panel range was 0.024-0.302, so this leaves real headroom
+LOGS_MIN = -7.0         # panel low was -5.42
+
+# Electrophiles that form a covalent bond with the catalytic residue. Season 1 excludes
+# them: they are a different medicinal-chemistry problem, and a docking-based score
+# rewards raw reactivity in ways that are easy to game.
+WARHEADS = [
+    # A nitrile on its own is not a warhead. Teriflunomide is an approved, non-covalent
+    # DHODH inhibitor and a bare [CX2]#[NX1] pattern rejected it - the same mistake as
+    # gating on hERG, caught the same way, by running an approved drug through first.
+    # What actually reacts with a catalytic cysteine is the peptidyl nitrile: the nitrile
+    # carbon sitting on an sp3 centre that carries the amide nitrogen, as in nirmatrelvir.
+    ("peptidyl nitrile", "[NX3][CX4][CX2]#[NX1]"),
+    # Michael acceptors must be terminal to react. The general C=C-C(=O)N pattern also
+    # matches teriflunomide, whose alkene is an enol stabilised by an adjacent nitrile
+    # and hydroxyl - an approved drug, and not an electrophile.
+    ("acrylamide",      "[CH2X3]=[CHX3][CX3](=O)[NX3]"),
+    ("vinyl sulfone",   "[CX3]=[CX3][SX4](=O)(=O)"),
+    ("aldehyde",        "[CX3H1](=O)[#6]"),
+    ("epoxide",         "[OX2r3]1[#6r3][#6r3]1"),
+    ("aziridine",       "[NX3r3]1[#6r3][#6r3]1"),
+    ("haloacetamide",   "[NX3][CX3](=O)[CH2][F,Cl,Br,I]"),
+    ("boronic acid",    "[BX3]([OX2H1])[OX2H1]"),
+    ("alpha-keto amide", "[CX3](=O)[CX3](=O)[NX3]"),
+]
+_WARHEADS = [(n, Chem.MolFromSmarts(s)) for n, s in WARHEADS]
+
+
+def canonical(text):
+    """Accept SMILES or InChI. A molecular formula cannot be accepted - too many isomers."""
+    t = (text or "").strip()
+    if not t:
+        return None, "빈 입력"
+    m = Chem.MolFromInchi(t) if t.upper().startswith("INCHI=") else Chem.MolFromSmiles(t)
+    if m is None:
+        return None, "구조를 해석할 수 없습니다 (SMILES 또는 InChI로 제출하세요; 분자식은 이성질체가 많아 평가 불가)"
+    return m, None
+
+
+def check(text, ames=None, logs=None, known_inchikeys=(), covalent_rule=True):
+    """Return a verdict dict. `ames`/`logs` come from the ADMET engine; omit them and
+    those two gates are simply reported as not evaluated rather than silently passed.
+
+    `covalent_rule` is target-scoped on purpose. Excluding covalent binders makes sense
+    for Mpro, where warheads react with a catalytic cysteine and a docking score can be
+    gamed by raw reactivity. PfDHODH is not inhibited that way, so for Season 1 the rule
+    buys nothing and only creates false rejections - two approved drugs were wrongly
+    turned away here before the patterns were tightened."""
+    m, err = canonical(text)
+    if m is None:
+        return {"admitted": False, "reject": [err], "relegate": []}
+
+    smi = Chem.MolToSmiles(m)
+    key = Chem.MolToInchiKey(m)
+    mw = Descriptors.MolWt(m)
+    heavy = m.GetNumHeavyAtoms()
+
+    reject, relegate, notes = [], [], []
+
+    for name, patt in (_WARHEADS if covalent_rule else []):
+        if patt is not None and m.HasSubstructMatch(patt):
+            reject.append("공유결합 warhead 검출 (%s) — Season 1은 비공유 트랙입니다" % name)
+            break
+
+    if mw > MW_MAX:
+        reject.append("분자량 %.1f > %.0f" % (mw, MW_MAX))
+    if heavy > HEAVY_MAX:
+        reject.append("무거운 원자 %d > %d" % (heavy, HEAVY_MAX))
+
+    hits = _PAINS.GetMatches(m)
+    if hits:
+        reject.append("PAINS 구조 (%s)" % ", ".join(h.GetDescription() for h in hits)[:80])
+
+    if key in set(known_inchikeys):
+        reject.append("기존 제출 또는 기준물질과 동일한 구조입니다")
+
+    # ADMET does not reject. It relegates: full score, shown, but below every clean entry.
+    if ames is None:
+        notes.append("Ames 미평가")
+    elif ames > AMES_MAX:
+        relegate.append("변이원성(Ames) %.3f > %.2f" % (ames, AMES_MAX))
+    if logs is None:
+        notes.append("용해도 미평가")
+    elif logs < LOGS_MIN:
+        relegate.append("극단적 불용성 (logS %.2f < %.1f)" % (logs, LOGS_MIN))
+
+    return {"admitted": not reject, "reject": reject, "relegate": relegate,
+            "notes": notes, "smiles": smi, "inchikey": key,
+            "mw": round(mw, 2), "heavy_atoms": heavy}
+
+
+if __name__ == "__main__":
+    import json, os, sys
+    # the Windows console defaults to cp949 here and dies on the em-dash in a reject reason
+    try:
+        sys.stdout.reconfigure(encoding="utf-8")
+    except Exception:
+        pass
+    A = json.load(open(os.path.join("data", "anchors.json"), encoding="utf-8"))
+    print("%-30s %-9s %-7s %-6s %s" % ("compound", "admitted", "MW", "heavy", "reason"))
+    print("-" * 100)
+    for a in A["anchors"]:
+        ad = a.get("measured_admet", {})
+        v = check(a["smiles"], ames=ad.get("ames"), logs=ad.get("solubility-aqsoldb"))
+        why = "; ".join(v["reject"] + ["[강등] " + r for r in v["relegate"]]) or "-"
+        print("%-30s %-9s %-7s %-6s %s"
+              % (a["label"][:29], "PASS" if v["admitted"] else "REJECT",
+                 v.get("mw"), v.get("heavy_atoms"), why[:60]))

index.html

@@ -0,0 +1,167 @@
+<!doctype html>
+<meta charset="utf-8">
+<title>Open Discovery Challenge #1 Malaria</title>
+<meta name="viewport" content="width=device-width,initial-scale=1">
+<style>
+  :root{
+    --bg:#0e1116; --panel:#161b23; --line:#252c38; --ink:#e6edf5; --muted:#8b98ab;
+    --accent:#2fe7d6; --anchor:#f0b429; --bad:#e5534b; --ok:#3fb950;
+  }
+  *{box-sizing:border-box}
+  body{margin:0;background:var(--bg);color:var(--ink);
+       font:15px/1.6 -apple-system,"Segoe UI",Roboto,"Malgun Gothic",sans-serif}
+  .wrap{max-width:1120px;margin:0 auto;padding:28px 18px 80px}
+  header{border-bottom:1px solid var(--line);padding-bottom:18px;margin-bottom:26px}
+  h1{margin:0 0 4px;font-size:26px;letter-spacing:-.2px}
+  h1 small{color:var(--accent);font-size:13px;letter-spacing:2px;display:block;
+           text-transform:uppercase;margin-bottom:6px;font-weight:600}
+  .sub{color:var(--muted);font-size:13.5px;margin:0}
+  .grid{display:grid;grid-template-columns:1fr 340px;gap:22px;align-items:start}
+  @media(max-width:900px){.grid{grid-template-columns:1fr}}
+  .card{background:var(--panel);border:1px solid var(--line);border-radius:12px;padding:16px 18px}
+  .card h2{margin:0 0 12px;font-size:14px;letter-spacing:1.2px;text-transform:uppercase;color:var(--muted)}
+  table{width:100%;border-collapse:collapse;font-size:13.5px}
+  th{text-align:right;color:var(--muted);font-weight:600;font-size:11px;
+     letter-spacing:.6px;text-transform:uppercase;padding:0 8px 8px;border-bottom:1px solid var(--line)}
+  th:nth-child(-n+3){text-align:left}
+  td{padding:9px 8px;border-bottom:1px solid rgba(255,255,255,.04);text-align:right}
+  td:nth-child(-n+3){text-align:left}
+  tr.anchor{background:rgba(240,180,41,.07)}
+  tr.anchor td{color:#f4d089}
+  tr.tier2{opacity:.65}
+  .rk{width:38px;font-variant-numeric:tabular-nums;color:var(--muted)}
+  .cid{font-family:ui-monospace,Menlo,Consolas,monospace;font-size:12.5px}
+  .tot{font-weight:700;font-size:15px;font-variant-numeric:tabular-nums}
+  .who{color:var(--muted);font-size:12.5px}
+  .badge{display:inline-block;font-size:10px;letter-spacing:.6px;padding:2px 6px;
+         border-radius:5px;background:rgba(240,180,41,.16);color:var(--anchor);margin-left:6px}
+  .badge.rel{background:rgba(229,83,75,.15);color:var(--bad)}
+  label{display:block;font-size:12px;color:var(--muted);margin:12px 0 4px;letter-spacing:.4px}
+  input,textarea{width:100%;background:#0d1117;border:1px solid var(--line);border-radius:8px;
+                 color:var(--ink);padding:9px 11px;font:inherit;font-size:13.5px}
+  textarea{resize:vertical;min-height:56px}
+  button{width:100%;margin-top:16px;background:var(--accent);color:#06231f;border:0;
+         border-radius:8px;padding:11px;font:inherit;font-weight:700;cursor:pointer}
+  button:disabled{opacity:.5;cursor:default}
+  .msg{margin-top:12px;font-size:12.5px;padding:10px 12px;border-radius:8px;display:none}
+  .msg.ok{display:block;background:rgba(63,185,80,.12);color:var(--ok)}
+  .msg.err{display:block;background:rgba(229,83,75,.12);color:var(--bad)}
+  .note{color:var(--muted);font-size:11.5px;line-height:1.65;margin-top:14px;
+        border-top:1px solid var(--line);padding-top:12px}
+  .wts{display:flex;flex-wrap:wrap;gap:6px;margin-top:8px}
+  .wts span{font-size:11px;color:var(--muted);background:#0d1117;border:1px solid var(--line);
+            border-radius:20px;padding:3px 10px}
+</style>
+
+<div class="wrap">
+  <header>
+    <h1><small>Open Discovery Challenge</small>#1 &nbsp;Malaria</h1>
+    <p class="sub">
+      AI가 제안한 저분자 후보를 공개된 기준으로 자동 채점하는 개방형 신약 발굴 대회.
+      표적은 <b>PfDHODH</b>(말라리아 원충 효소), 역표적은 <b>사람 DHODH</b>입니다.
+    </p>
+    <div class="wts" id="wts"></div>
+  </header>
+
+  <div class="grid">
+    <div class="card">
+      <h2>순위표 <span id="counts" style="float:right;font-size:11px"></span></h2>
+      <table>
+        <thead><tr>
+          <th class="rk">#</th><th>후보</th><th>제출자 / 모델</th>
+          <th>약효</th><th>결합</th><th>선택성</th><th>ADMET</th><th>신규</th><th>합성</th><th>총점</th>
+        </tr></thead>
+        <tbody id="rows"><tr><td colspan="10" class="who">불러오는 중…</td></tr></tbody>
+      </table>
+      <div class="note">
+        기준물질(노란 행)은 점수를 받되 <b>등수를 갖지 않습니다</b>. 척도를 눈으로 확인하시라고 넣은 것입니다.<br>
+        구조는 전체 공개하지 않습니다. 골격 해시와 분자량 구간만 표시되며, 원본은 비공개로 보관됩니다.<br>
+        점수는 <b>계산 기반 후보 평가</b>이며 실제 효능·안전성이나 승인약과의 우열을 뜻하지 않습니다.
+      </div>
+    </div>
+
+    <div class="card">
+      <h2>제출</h2>
+      <label>분자 구조식 (SMILES 또는 InChI)</label>
+      <input id="structure" placeholder="예: CC1=NC2=NC(=NN2C(=C1)N...)">
+      <label>표시 ID (이름·소속·닉네임)</label>
+      <input id="display_name" placeholder="공개 순위표에 표시됩니다">
+      <label>사용 모델명 (선택)</label>
+      <input id="model_name" placeholder="예: anthropic/claude-sonnet, Qwen/…, 직접 설계">
+      <label>설계 근거 (선택)</label>
+      <textarea id="rationale" placeholder="왜 이 구조인지 간단히"></textarea>
+      <button id="go">제출</button>
+      <div class="msg" id="msg"></div>
+      <div class="note">
+        분자식(C20H25N3O4 등)은 받지 않습니다 — 이성질체가 너무 많아 평가가 불가능합니다.<br>
+        제출 즉시 구조 검사를 거치고, 채점은 GPU 작업 대기열에서 처리됩니다(수 분 소요).
+      </div>
+    </div>
+  </div>
+</div>
+
+<script>
+const $ = s => document.querySelector(s);
+const AX = ["activity","binding","selectivity","admet","novelty","synthesis"];
+const f1 = v => (v==null||v==="") ? "–" : (+v).toFixed(1);
+
+async function load(){
+  const d = await (await fetch("api/leaderboard")).json();
+  $("#wts").innerHTML = Object.entries(d.season.weights)
+    .map(([k,v]) => `<span>${k} ${v}</span>`).join("");
+  $("#counts").textContent = `제출 ${d.counts.scored} · 기준물질 ${d.counts.anchors}`;
+
+  const tb = $("#rows");
+  if(!d.entries.length){ tb.innerHTML = '<tr><td colspan="10" class="who">아직 채점된 제출이 없습니다.</td></tr>'; return; }
+  tb.innerHTML = d.entries.map(e => {
+    const a = e.axes || {};
+    const cls = [e.is_anchor ? "anchor" : "", e.tier===2 ? "tier2" : ""].join(" ").trim();
+    const who = e.is_anchor ? (e.note||"기준물질")
+              : `${e.display_name||"–"}${e.model_name?` <span class="who">· ${e.model_name}</span>`:""}`;
+    const id = e.is_anchor ? e.candidate_id
+             : `<span class="cid">${e.candidate_id}</span>` +
+               (e.skeleton?` <span class="who">${e.skeleton}</span>`:"");
+    const flag = e.is_anchor ? '<span class="badge">기준</span>'
+               : (e.tier===2 ? '<span class="badge rel">강등</span>' : "");
+    return `<tr class="${cls}">
+      <td class="rk">${e.rank ?? "—"}</td>
+      <td>${id}${flag}</td><td>${who}</td>
+      ${AX.map(k=>`<td>${f1(a[k])}</td>`).join("")}
+      <td class="tot">${f1(e.total)}</td></tr>`;
+  }).join("");
+}
+
+$("#go").onclick = async () => {
+  const btn = $("#go"), msg = $("#msg");
+  const body = {
+    structure: $("#structure").value.trim(),
+    display_name: $("#display_name").value.trim(),
+    model_name: $("#model_name").value.trim(),
+    rationale: $("#rationale").value.trim(),
+  };
+  if(!body.structure || !body.display_name){
+    msg.className = "msg err"; msg.textContent = "구조와 표시 ID는 필수입니다."; return;
+  }
+  btn.disabled = true; msg.className = "msg"; msg.textContent = "";
+  try{
+    const r = await fetch("api/submit", {method:"POST",
+      headers:{"Content-Type":"application/json"}, body: JSON.stringify(body)});
+    const d = await r.json();
+    if(d.accepted){
+      msg.className = "msg ok";
+      msg.textContent = `접수되었습니다 · ${d.candidate_id} · 대기 ${d.queue_position}건. ${d.note}`;
+      $("#structure").value = "";
+      load();
+    }else{
+      msg.className = "msg err";
+      msg.textContent = (d.reasons||["제출이 거부되었습니다"]).join(" / ");
+    }
+  }catch(e){
+    msg.className = "msg err"; msg.textContent = "요청 실패: " + e;
+  }
+  btn.disabled = false;
+};
+
+load();
+setInterval(load, 20000);
+</script>

requirements.txt

@@ -0,0 +1,4 @@
+fastapi==0.115.6
+uvicorn[standard]==0.34.0
+pydantic==2.10.4
+rdkit==2024.9.4