def _validate_reacting_mol(self):
reacting_mol = Chem.MolFromSmiles(Chem.MolToSmiles(self.reacting_mol))
if not reacting_mol.GetSubstructMatch(self.INDOLE) or not isinstance(
self.model, models.Sidechain):
raise InvalidMolecule(
'The reacting molecule in a pyrroloindoline reaction must be a sidechain containing an indole!'
)
def _validate_reacting_atom(self, atom):
if atom.GetSymbol() != 'C' or atom.GetTotalNumHs(
) == 0 or not atom.GetIsAromatic():
raise InvalidMolecule(
'The nucleophilic reacting atom must be an aromatic carbon with at least one hydrogen for a pictet spangler reaction!'
)
self.reacting_atom = atom
def _process_nucleophile(self):
if isinstance(self.model, models.Sidechain):
self._tag_sidechain_connection_atom()
elif isinstance(self.model, models.Monomer):
self._tag_monomer_connection_atom()
else:
raise InvalidMolecule(
f'The nucleophile needs to be an instance of a sidechain or a monomer!'
)
def _initialize(self, reacting_mol):
super()._initialize(reacting_mol)
try:
self.reacting_mol = reacting_mol.aldehyde_cyclization_mol
if self.reacting_mol is None:
raise AttributeError
except AttributeError:
raise InvalidMolecule(
'The reactin mol must be a template with an aldehyde_cyclization_mol property that is not None!'
)
def _initialize(self, reacting_mol):
super()._initialize(reacting_mol)
try:
self.reacting_mol = reacting_mol.template_pictet_spangler_mol
if self.reacting_mol is None:
raise AttributeError
except AttributeError:
raise InvalidMolecule(
'The reacting mol must be a template with a template_pictet_spangler_mol property that is not None!'
)
def _validate_sidechain(self):
connection_atom = utils.get_atom_with_map_num(
self.reacting_mol, self.SIDECHAIN_OLIGOMERIZATION_MAP_NUM)
paths = Chem.FindAllPathsOfLengthN(
self.reacting_mol,
3,
useBonds=False,
rootedAtAtom=self.reacting_atom.GetIdx())
atoms = set().union([atom for path in paths for atom in path])
if connection_atom.GetIdx() not in atoms - set(
atom.GetIdx() for atom in connection_atom.GetNeighbors()):
raise InvalidMolecule(
'The attachment point of the reacting sidechain must be two atoms away from the reacting atom in a pictet spangler reaction!'
)
def _validate_monomer(self):
try:
n_term_atom = utils.get_atom_with_map_num(
self.reacting_mol, self.BACKBONE_NITROGEN_MAP_NUM)
paths = Chem.FindAllPathsOfLengthN(
self.reacting_mol,
5,
useBonds=False,
rootedAtAtom=self.reacting_atom.GetIdx())
atoms = set().union([atom for path in paths for atom in path])
if n_term_atom.GetIdx() not in atoms - set(
atom.GetIdx() for atom in n_term_atom.GetNeighbors()):
raise InvalidMolecule(
'The reacting atom in the monomer must be 4 atoms away from the N-terminus!'
)
except (AttributeError, RuntimeError):
raise InvalidMolecule
def _validate_reacting_atom(self, atom):
self._tag_sidechain_connection_atom(change_to_wildcard=False)
num_neighbors_hydrogens = [
neighbor.GetTotalNumHs() for neighbor in atom.GetNeighbors()
]
connection_atom = self._get_connection_atom()
connection_atom_neighbors = [
neighbor.GetIdx() for neighbor in connection_atom.GetNeighbors()
]
# reaction initiated at carbon that is the attachment point to amino acid backbone, which contains no hydrogens
if atom.GetTotalNumHs() != 0 \
or atom.GetSymbol() != 'C' \
or 1 not in num_neighbors_hydrogens \
or atom.GetIdx() not in connection_atom_neighbors:
raise InvalidMolecule(
'The reacting atom of a pyrroloindoline reaction must be an aromatic carbon with no'
' hydrogens, adjacent to the connecting atom between the sidechain and backbone, and'
' with a neighbor that has exactly one hydrogen.')
def _validate_template(self):
if self.template is None or not self.template.GetSubstructMatch(
self.REQUIRED_SUBSTRUCT):
raise InvalidMolecule(
'The template molecule must contain a "C=CC" substructure for a pyrroloindoline reaction!'
)
def _validate_reacting_atom(self, atom):
if atom.GetSymbol() not in ('N', 'O',
'S') or atom.GetTotalNumHs() == 0:
raise InvalidMolecule(
'The nucleophilic reacting atom must be a heteroatom with at least one hydrogen for a tsuji trost reaction!'
)