File size: 1,764 Bytes
c289d87 | 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 | from __future__ import annotations
from pathlib import Path
from rdkit import Chem
from rdkit.Chem import AllChem
def _embed_3d_with_retries(mol: Chem.Mol) -> bool:
"""Try multiple RDKit embedding strategies to guarantee a 3D conformer."""
attempts = []
p1 = AllChem.ETKDGv3()
p1.randomSeed = 42
attempts.append(p1)
p2 = AllChem.ETKDGv2()
p2.randomSeed = 42
attempts.append(p2)
p3 = AllChem.ETKDGv3()
p3.randomSeed = 42
p3.useRandomCoords = True
attempts.append(p3)
for params in attempts:
try:
mol.RemoveAllConformers()
status = AllChem.EmbedMolecule(mol, params)
if int(status) != 0:
continue
if mol.GetNumConformers() == 0:
continue
try:
AllChem.UFFOptimizeMolecule(mol, maxIters=300)
except Exception:
# Keep conformer if optimization fails.
pass
return bool(mol.GetConformer().Is3D())
except Exception:
continue
return False
def prepare_ligand_sdf(ligand_id: str, smiles: str, out_path: str | Path) -> Path:
"""Prepare ligand SDF with optional 3D coordinates for docking."""
mol = Chem.MolFromSmiles(smiles)
if mol is None:
raise ValueError(f"Invalid SMILES for ligand {ligand_id}: {smiles}")
mol = Chem.AddHs(mol)
has_3d = _embed_3d_with_retries(mol)
if not has_3d:
raise ValueError(f"Failed to generate 3D conformer for ligand {ligand_id}")
mol.SetProp("_Name", ligand_id)
target = Path(out_path)
target.parent.mkdir(parents=True, exist_ok=True)
writer = Chem.SDWriter(str(target))
writer.write(mol)
writer.close()
return target
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