lingyuzeng
46a438dd36
- skip fused/shared/multi-anchor side systems during extraction - add fragment library schema and fragment_library.csv export - make scaffold prep strict for non-spliceable positions
304 lines
9.0 KiB
Python
304 lines
9.0 KiB
Python
from __future__ import annotations
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from dataclasses import dataclass
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from typing import Mapping
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from rdkit import Chem
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@dataclass(frozen=True)
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class BuiltMacrolactone:
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mol: Chem.Mol
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smiles: str
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position_to_atom: dict[int, int]
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def build_macrolactone(
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ring_size: int,
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side_chains: Mapping[int, str] | None = None,
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ring_atom_symbols: Mapping[int, str] | None = None,
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) -> BuiltMacrolactone:
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if not 12 <= ring_size <= 20:
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raise ValueError("ring_size must be between 12 and 20")
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side_chains = dict(side_chains or {})
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ring_atom_symbols = dict(ring_atom_symbols or {})
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rwmol = Chem.RWMol()
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position_to_atom: dict[int, int] = {
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1: rwmol.AddAtom(Chem.Atom("C")),
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2: rwmol.AddAtom(Chem.Atom("O")),
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}
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for position in range(3, ring_size + 1):
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position_to_atom[position] = rwmol.AddAtom(Chem.Atom(ring_atom_symbols.get(position, "C")))
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carbonyl_oxygen_idx = rwmol.AddAtom(Chem.Atom("O"))
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rwmol.AddBond(position_to_atom[1], position_to_atom[2], Chem.BondType.SINGLE)
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for position in range(2, ring_size):
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rwmol.AddBond(
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position_to_atom[position],
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position_to_atom[position + 1],
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Chem.BondType.SINGLE,
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)
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rwmol.AddBond(position_to_atom[ring_size], position_to_atom[1], Chem.BondType.SINGLE)
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rwmol.AddBond(position_to_atom[1], carbonyl_oxygen_idx, Chem.BondType.DOUBLE)
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for position, side_chain in side_chains.items():
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if position not in position_to_atom:
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raise ValueError(f"Invalid ring position: {position}")
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_add_side_chain(rwmol, position_to_atom[position], side_chain)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom=position_to_atom,
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)
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def build_ambiguous_smiles() -> str:
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mol_12 = build_macrolactone(12).mol
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mol_14 = build_macrolactone(14).mol
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combined = Chem.CombineMols(mol_12, mol_14)
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return Chem.MolToSmiles(combined, isomericSmiles=True)
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def build_non_standard_ring_atom_macrolactone(
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ring_size: int = 16,
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hetero_position: int = 5,
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atom_symbol: str = "N",
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) -> BuiltMacrolactone:
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if hetero_position < 3 or hetero_position > ring_size:
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raise ValueError("hetero_position must be between 3 and ring_size")
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return build_macrolactone(
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ring_size=ring_size,
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ring_atom_symbols={hetero_position: atom_symbol},
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)
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def build_macrolactone_with_fused_side_ring(
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ring_size: int = 16,
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fused_positions: tuple[int, int] = (5, 6),
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side_chains: Mapping[int, str] | None = None,
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) -> BuiltMacrolactone:
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base = build_macrolactone(ring_size=ring_size, side_chains=side_chains)
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position_a, position_b = fused_positions
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rwmol = Chem.RWMol(Chem.Mol(base.mol))
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atom_x = rwmol.AddAtom(Chem.Atom("C"))
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atom_y = rwmol.AddAtom(Chem.Atom("C"))
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rwmol.AddBond(base.position_to_atom[position_a], atom_x, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_x, atom_y, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_y, base.position_to_atom[position_b], Chem.BondType.SINGLE)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom=base.position_to_atom,
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)
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def build_macrolactone_with_bridge_side_chain(
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ring_size: int = 16,
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bridge_positions: tuple[int, int] = (5, 8),
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side_chains: Mapping[int, str] | None = None,
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) -> BuiltMacrolactone:
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base = build_macrolactone(ring_size=ring_size, side_chains=side_chains)
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position_a, position_b = bridge_positions
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rwmol = Chem.RWMol(Chem.Mol(base.mol))
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atom_x = rwmol.AddAtom(Chem.Atom("C"))
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atom_y = rwmol.AddAtom(Chem.Atom("C"))
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rwmol.AddBond(base.position_to_atom[position_a], atom_x, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_x, atom_y, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_y, base.position_to_atom[position_b], Chem.BondType.SINGLE)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom=base.position_to_atom,
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)
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def build_macrolactone_with_shared_atom_side_ring(
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ring_size: int = 16,
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position: int = 5,
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side_chains: Mapping[int, str] | None = None,
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) -> BuiltMacrolactone:
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base = build_macrolactone(ring_size=ring_size, side_chains=side_chains)
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rwmol = Chem.RWMol(Chem.Mol(base.mol))
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atom_x = rwmol.AddAtom(Chem.Atom("C"))
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atom_y = rwmol.AddAtom(Chem.Atom("C"))
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atom_z = rwmol.AddAtom(Chem.Atom("C"))
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ring_atom_idx = base.position_to_atom[position]
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rwmol.AddBond(ring_atom_idx, atom_x, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_x, atom_y, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_y, atom_z, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_z, ring_atom_idx, Chem.BondType.SINGLE)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom=base.position_to_atom,
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)
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def build_macrolactone_with_single_anchor_side_ring(
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ring_size: int = 16,
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position: int = 5,
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side_chains: Mapping[int, str] | None = None,
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) -> BuiltMacrolactone:
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base = build_macrolactone(ring_size=ring_size, side_chains=side_chains)
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rwmol = Chem.RWMol(Chem.Mol(base.mol))
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atom_x = rwmol.AddAtom(Chem.Atom("C"))
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atom_y = rwmol.AddAtom(Chem.Atom("C"))
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atom_z = rwmol.AddAtom(Chem.Atom("C"))
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ring_atom_idx = base.position_to_atom[position]
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rwmol.AddBond(ring_atom_idx, atom_x, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_x, atom_y, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_y, atom_z, Chem.BondType.SINGLE)
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rwmol.AddBond(atom_z, atom_x, Chem.BondType.SINGLE)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom=base.position_to_atom,
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)
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def build_overlapping_candidate_macrolactone() -> BuiltMacrolactone:
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rwmol = Chem.RWMol()
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atom_labels = (
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"A1",
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"A2",
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"S1",
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"S2",
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"S3",
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"S4",
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"A5",
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"A6",
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"A7",
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"A8",
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"A9",
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"A10",
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"B1",
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"B2",
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"B5",
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"B6",
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"B7",
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"B8",
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"B9",
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"B10",
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"AO",
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"BO",
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)
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atom_symbols = {
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"A1": "C",
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"A2": "O",
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"S1": "C",
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"S2": "C",
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"S3": "C",
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"S4": "C",
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"A5": "C",
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"A6": "C",
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"A7": "C",
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"A8": "C",
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"A9": "C",
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"A10": "C",
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"B1": "C",
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"B2": "O",
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"B5": "C",
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"B6": "C",
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"B7": "C",
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"B8": "C",
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"B9": "C",
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"B10": "C",
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"AO": "O",
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"BO": "O",
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}
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atoms = {label: rwmol.AddAtom(Chem.Atom(atom_symbols[label])) for label in atom_labels}
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for atom_a, atom_b in (
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("A1", "A2"),
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("A2", "S1"),
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("S1", "S2"),
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("S2", "S3"),
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("S3", "S4"),
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("S4", "A5"),
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("A5", "A6"),
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("A6", "A7"),
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("A7", "A8"),
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("A8", "A9"),
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("A9", "A10"),
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("A10", "A1"),
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("B1", "B2"),
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("B2", "S1"),
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("S4", "B5"),
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("B5", "B6"),
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("B6", "B7"),
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("B7", "B8"),
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("B8", "B9"),
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("B9", "B10"),
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("B10", "B1"),
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):
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rwmol.AddBond(atoms[atom_a], atoms[atom_b], Chem.BondType.SINGLE)
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rwmol.AddBond(atoms["A1"], atoms["AO"], Chem.BondType.DOUBLE)
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rwmol.AddBond(atoms["B1"], atoms["BO"], Chem.BondType.DOUBLE)
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mol = rwmol.GetMol()
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Chem.SanitizeMol(mol)
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return BuiltMacrolactone(
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mol=mol,
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smiles=Chem.MolToSmiles(mol, isomericSmiles=True),
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position_to_atom={},
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)
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def canonicalize(smiles_or_mol: str | Chem.Mol) -> str:
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if isinstance(smiles_or_mol, Chem.Mol):
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mol = smiles_or_mol
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else:
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mol = Chem.MolFromSmiles(smiles_or_mol)
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if mol is None:
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raise ValueError(f"Unable to parse SMILES: {smiles_or_mol}")
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return Chem.MolToSmiles(mol, isomericSmiles=True)
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def _add_side_chain(rwmol: Chem.RWMol, ring_atom_idx: int, side_chain: str) -> None:
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if side_chain == "methyl":
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carbon_idx = rwmol.AddAtom(Chem.Atom("C"))
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rwmol.AddBond(ring_atom_idx, carbon_idx, Chem.BondType.SINGLE)
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return
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if side_chain == "ethyl":
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carbon_1_idx = rwmol.AddAtom(Chem.Atom("C"))
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carbon_2_idx = rwmol.AddAtom(Chem.Atom("C"))
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rwmol.AddBond(ring_atom_idx, carbon_1_idx, Chem.BondType.SINGLE)
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rwmol.AddBond(carbon_1_idx, carbon_2_idx, Chem.BondType.SINGLE)
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return
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if side_chain == "exocyclic_alkene":
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carbon_1_idx = rwmol.AddAtom(Chem.Atom("C"))
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carbon_2_idx = rwmol.AddAtom(Chem.Atom("C"))
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rwmol.AddBond(ring_atom_idx, carbon_1_idx, Chem.BondType.DOUBLE)
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rwmol.AddBond(carbon_1_idx, carbon_2_idx, Chem.BondType.SINGLE)
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return
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raise ValueError(f"Unsupported side chain: {side_chain}")
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