| |
| from __future__ import annotations |
|
|
| import argparse |
| import csv |
| from pathlib import Path |
|
|
|
|
| MANUAL_CANDIDATES = [ |
| { |
| "pdb_id": "1IEP", |
| "receptor_chain": "A", |
| "ligand_resname": "STI", |
| "ligand_chain": "A", |
| "ligand_id": "STI", |
| "ligand_smiles": "CC1=NC(NC2=CC(=C(C=C2)Cl)NC3=NC=CC(=N3)C4=CN=CC=C4)=CC(=N1)N", |
| "pubchem_cid": "5291", |
| "ligand_heavy_atoms": 41, |
| "ligand_mw": 493.6, |
| "estimated_pubchem_hits_0.99_0.30": 650000, |
| "notes": "Heuristic large-chemotype kinase inhibitor candidate; requires server-side validation of crawl volume.", |
| "recommended": True, |
| }, |
| { |
| "pdb_id": "3PTB", |
| "receptor_chain": "A", |
| "ligand_resname": "BEN", |
| "ligand_chain": "A", |
| "ligand_id": "BEN", |
| "ligand_smiles": "c1(ccccc1)C(=N)N", |
| "pubchem_cid": "2332", |
| "ligand_heavy_atoms": 9, |
| "ligand_mw": 120.15, |
| "estimated_pubchem_hits_0.99_0.30": 550000, |
| "notes": "Empirically validated PubChem crawl to 50k on local machine; ligand is small so pocket chemistry is broad but benchmark realism is weaker.", |
| "recommended": True, |
| }, |
| { |
| "pdb_id": "4WKQ", |
| "receptor_chain": "A", |
| "ligand_resname": "IRE", |
| "ligand_chain": "A", |
| "ligand_id": "IRE", |
| "ligand_smiles": "", |
| "pubchem_cid": "", |
| "ligand_heavy_atoms": 28, |
| "ligand_mw": 430.0, |
| "estimated_pubchem_hits_0.99_0.30": 7000, |
| "notes": "Observed narrow chemotype in current pipeline; not suitable for very large similarity benchmark.", |
| "recommended": False, |
| }, |
| { |
| "pdb_id": "4HG7", |
| "receptor_chain": "A", |
| "ligand_resname": "NUT", |
| "ligand_chain": "A", |
| "ligand_id": "NUT", |
| "ligand_smiles": "", |
| "pubchem_cid": "", |
| "ligand_heavy_atoms": 33, |
| "ligand_mw": 500.0, |
| "estimated_pubchem_hits_0.99_0.30": 0, |
| "notes": "Current PubChem similarity path was unstable for this ligand in prior tests.", |
| "recommended": False, |
| }, |
| ] |
|
|
|
|
| def build_parser() -> argparse.ArgumentParser: |
| parser = argparse.ArgumentParser(description="Write a TSV of candidate PDB ligand complexes for large PubChem similarity crawls.") |
| parser.add_argument("--out", required=True) |
| parser.add_argument("--max-candidates", type=int, default=50) |
| parser.add_argument("--min-heavy-atoms", type=int, default=15) |
| parser.add_argument("--max-heavy-atoms", type=int, default=60) |
| parser.add_argument("--min-estimated-hits", type=int, default=500000) |
| return parser |
|
|
|
|
| def main() -> int: |
| args = build_parser().parse_args() |
| out = Path(args.out) |
| out.parent.mkdir(parents=True, exist_ok=True) |
| rows = [] |
| for row in MANUAL_CANDIDATES: |
| item = dict(row) |
| heavy = int(item["ligand_heavy_atoms"]) |
| hits = int(item["estimated_pubchem_hits_0.99_0.30"]) |
| if heavy < int(args.min_heavy_atoms) or heavy > int(args.max_heavy_atoms): |
| item["recommended"] = False |
| item["notes"] += " Filtered by heavy atom window." |
| if hits < int(args.min_estimated_hits): |
| item["recommended"] = False |
| item["notes"] += " Estimated hit count below requested large-run threshold." |
| rows.append(item) |
| rows = rows[: max(1, int(args.max_candidates))] |
| with out.open("w", encoding="utf-8", newline="") as handle: |
| writer = csv.DictWriter( |
| handle, |
| fieldnames=[ |
| "pdb_id", |
| "receptor_chain", |
| "ligand_resname", |
| "ligand_chain", |
| "ligand_id", |
| "ligand_smiles", |
| "pubchem_cid", |
| "ligand_heavy_atoms", |
| "ligand_mw", |
| "estimated_pubchem_hits_0.99_0.30", |
| "notes", |
| "recommended", |
| ], |
| delimiter="\t", |
| ) |
| writer.writeheader() |
| writer.writerows(rows) |
| print(out) |
| return 0 |
|
|
|
|
| if __name__ == "__main__": |
| raise SystemExit(main()) |
|
|
