File size: 4,165 Bytes
504d922 | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 | #!/usr/bin/env python3
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())
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