def _getFlippers(mol, options):
Chem.FindPotentialStereoBonds(mol)
flippers = []
if not options.onlyStereoGroups:
for atom in mol.GetAtoms():
if atom.HasProp("_ChiralityPossible"):
if (not options.onlyUnassigned or atom.GetChiralTag()
== Chem.ChiralType.CHI_UNSPECIFIED):
flippers.append(_AtomFlipper(atom))
for bond in mol.GetBonds():
bstereo = bond.GetStereo()
if bstereo != Chem.BondStereo.STEREONONE:
if (not options.onlyUnassigned
or bstereo == Chem.BondStereo.STEREOANY):
flippers.append(_BondFlipper(bond))
if options.onlyUnassigned:
# otherwise these will be counted twice
for group in mol.GetStereoGroups():
if group.GetGroupType() != Chem.StereoGroupType.STEREO_ABSOLUTE:
flippers.append(_StereoGroupFlipper(group))
return flippers
def change_stereobond_in_imine_to_cis(mol: Chem.Mol) -> Chem.Mol:
Chem.FindPotentialStereoBonds(mol)
for bond in mol.GetBonds():
if bond.GetStereo() == Chem.BondStereo.STEREOANY:
logger.debug(
f"{bond.GetBeginAtom().GetSymbol()} {bond.GetSmarts()} {bond.GetEndAtom().GetSymbol()}"
)
bond.SetStereo(Chem.BondStereo.STEREOZ)
return mol
def has_stereo_defined(molecule):
#ToDo Fix this function for carbons with explicit hydrogen and imine with implicit hydrogens
"""
Parameters
----------
molecule
Returns
-------
"""
unspec_chiral = False
unspec_db = False
problematic_atoms = list()
problematic_bonds = list()
# remove map indices and store. Then create molecule with SMILES without map indices and check for stereo on that.
# This step is needed because even when map indices are stored in the data of the atoms, it is used for assigning potential
# stereo centers. If a molecule does not have map indices but has data on the atoms, it will get flagged
had_atom_map = False
if has_atom_map(molecule):
had_atom_map = True
remove_atom_map(molecule)
a = Chem.rdmolfiles.SmilesParserParams()
a.removeHs = False
mol_copy = Chem.MolFromSmiles(Chem.MolToSmiles(molecule), a)
# restore map indices
if had_atom_map:
restore_atom_map(molecule)
chiral_centers = Chem.FindMolChiralCenters(mol_copy,
includeUnassigned=True)
for center in chiral_centers:
atom_id = center[0]
if center[-1] == '?':
unspec_chiral = True
problematic_atoms.append(
(atom_id, mol_copy.GetAtomWithIdx(atom_id).GetSmarts()))
# Find potential stereo bonds that are unspecified
Chem.FindPotentialStereoBonds(mol_copy)
for bond in mol_copy.GetBonds():
if bond.GetStereo() == Chem.BondStereo.STEREOANY:
unspec_db = True
problematic_bonds.append(
(bond.GetBeginAtom().GetSmarts(), bond.GetSmarts(),
bond.GetEndAtom().GetSmarts()))
if unspec_chiral or unspec_db:
warnings.warn(
"Stereochemistry is unspecified. Problematic atoms {}, problematic bonds {}"
.format(problematic_atoms, problematic_bonds))
return False
else:
return True
def enumerate_stereoisomers(
mol,
n_variants: int = 20,
undefined_only: bool = False,
rationalise: bool = True,
):
"""Enumerate the stereocenters and bonds of the current molecule.
Original source: the `openff-toolkit` lib.
Warning: this function can be computationnaly intensive.
Args:
mol: The molecule whose state we should enumerate.
n_variants: The maximum amount of molecules that should be returned.
undefined_only: If we should enumerate all stereocenters and bonds or only those
with undefined stereochemistry.
rationalise: If we should try to build and rationalise the molecule to ensure it
can exist.
"""
from rdkit.Chem.EnumerateStereoisomers import EnumerateStereoisomers
from rdkit.Chem.EnumerateStereoisomers import StereoEnumerationOptions
# safety first
mol = copy_mol(mol)
# in case any bonds/centers are missing stereo chem flag it here
Chem.AssignStereochemistry(mol, force=False, flagPossibleStereoCenters=True, cleanIt=True) # type: ignore
Chem.FindPotentialStereoBonds(mol, cleanIt=True) # type: ignore
# set up the options
stereo_opts = StereoEnumerationOptions(
tryEmbedding=rationalise,
onlyUnassigned=undefined_only,
maxIsomers=n_variants,
)
try:
isomers = tuple(EnumerateStereoisomers(mol, options=stereo_opts))
except:
# NOTE(hadim): often got "Stereo atoms should be specified before specifying CIS/TRANS bond stereochemistry"
# for the ligand of reference (coming from the PDB). Not sure how to handle that.
isomers = []
variants = []
for isomer in isomers:
# isomer has CIS/TRANS tags so convert back to E/Z
Chem.SetDoubleBondNeighborDirections(isomer) # type: ignore
Chem.AssignStereochemistry(isomer, force=True, cleanIt=True) # type: ignore
variants.append(isomer)
return variants
def _find_rd_stereocenters(
molecule: Molecule,
) -> Tuple[List[int], List[Tuple[int, int]]]:
"""A method which returns the of the stereogenic atom and bonds of a molecule
using the RDKit.
Parameters
----------
molecule
The molecule whose stereocenters should be returned.
Notes
-----
* This method currently deals with RDKit directly and should be removed once
the API points suggested in openff-toolkit issue #903 have been added.
Returns
-------
The indices of the stereogenic atoms in the molecule and the indices of the
atoms involved in stereogenic bonds in the molecule.
"""
from rdkit import Chem
rd_molecule = molecule.to_rdkit()
Chem.AssignStereochemistry(
rd_molecule, cleanIt=True, force=True, flagPossibleStereoCenters=True
)
stereogenic_atoms = {
atom.GetIdx()
for atom in rd_molecule.GetAtoms()
if atom.HasProp("_ChiralityPossible")
}
# Clear any previous assignments on the bonds, since FindPotentialStereo
# may not overwrite it
for bond in rd_molecule.GetBonds():
bond.SetStereo(Chem.BondStereo.STEREONONE)
Chem.FindPotentialStereoBonds(rd_molecule, cleanIt=True)
stereogenic_bonds = {
(bond.GetBeginAtomIdx(), bond.GetEndAtomIdx())
for bond in rd_molecule.GetBonds()
if bond.GetStereo() == Chem.BondStereo.STEREOANY
}
return sorted(stereogenic_atoms), sorted(stereogenic_bonds)
def decide_unspec_stereo(smiles: str) -> str:
m = Chem.MolFromSmiles(smiles)
m = Chem.AddHs(m)
Chem.FindPotentialStereoBonds(m)
for bond in m.GetBonds():
if bond.GetStereo() == Chem.BondStereo.STEREOANY:
print(
bond.GetBeginAtom().GetSymbol(),
bond.GetSmarts(),
bond.GetEndAtom().GetSymbol(),
)
bond.SetStereo(Chem.BondStereo.STEREOE)
return Chem.MolToSmiles(m)
def flag_unspec_stereo(smiles: str) -> bool:
m = Chem.MolFromSmiles(smiles)
m = Chem.AddHs(m)
unspec = False
Chem.FindPotentialStereoBonds(m)
for bond in m.GetBonds():
if bond.GetStereo() == Chem.BondStereo.STEREOANY:
logger.debug(
bond.GetBeginAtom().GetSymbol(),
bond.GetSmarts(),
bond.GetEndAtom().GetSymbol(),
)
unspec = True
return unspec
def _getFlippers(mol, options):
Chem.FindPotentialStereoBonds(mol)
flippers = []
for atom in mol.GetAtoms():
if atom.HasProp("_ChiralityPossible"):
if (not options.onlyUnassigned
or atom.GetChiralTag() == Chem.ChiralType.CHI_UNSPECIFIED):
flippers.append(_AtomFlipper(atom))
for bond in mol.GetBonds():
bstereo = bond.GetStereo()
if bstereo != Chem.BondStereo.STEREONONE:
if (not options.onlyUnassigned
or bstereo == Chem.BondStereo.STEREOANY):
flippers.append(_BondFlipper(bond))
return flippers
def has_stereo_defined(molecule):
"""
Parameters
----------
molecule
Returns
-------
"""
unspec_chiral = False
unspec_db = False
problematic_atoms = list()
problematic_bonds = list()
chiral_centers = Chem.FindMolChiralCenters(molecule,
includeUnassigned=True)
for center in chiral_centers:
atom_id = center[0]
if center[-1] == '?':
unspec_chiral = True
problematic_atoms.append(
(atom_id, molecule.GetAtomWithIdx(atom_id).GetSmarts()))
# Find potential stereo bonds that are unspecified
Chem.FindPotentialStereoBonds(molecule)
for bond in molecule.GetBonds():
if bond.GetStereo() == Chem.BondStereo.STEREOANY:
unspec_db = True
problematic_bonds.append(
(bond.GetBeginAtom().GetSmarts(), bond.GetSmarts(),
bond.GetEndAtom().GetSmarts()))
if unspec_chiral or unspec_db:
warnings.warn(
"Stereochemistry is unspecified. Problematic atoms {}, problematic bonds {}"
.format(problematic_atoms, problematic_bonds))
return False
else:
return True
