| 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 | |