#!/usr/bin/env python
# -*- coding: utf-8 -*-
# Rhizome
# Version beta 0.0, August 2023
# Property of IBM Research, Accelerated Discovery
#
"""
PLEASE NOTE THIS IMPLEMENTATION INCLUDES THE ORIGINAL SOURCE CODE (AND SOME ADAPTATIONS)
OF THE MHG IMPLEMENTATION OF HIROSHI KAJINO AT IBM TRL ALREADY PUBLICLY AVAILABLE.
THIS MIGHT INFLUENCE THE DECISION OF THE FINAL LICENSE SO CAREFUL CHECK NEEDS BE DONE.
"""
""" Title """
__author__ = "Hiroshi Kajino <KAJINO@jp.ibm.com>"
__copyright__ = "(c) Copyright IBM Corp. 2018"
__version__ = "0.1"
__date__ = "Jan 12 2018"
from copy import deepcopy
from rdkit import Chem
from rdkit import RDLogger
import networkx as nx
import numpy as np
from ..hypergraph import Hypergraph
from ..graph_grammar.symbols import TSymbol, BondSymbol
# supress warnings
lg = RDLogger.logger()
lg.setLevel(RDLogger.CRITICAL)
class HGGen(object):
"""
load .smi file and yield a hypergraph.
Attributes
----------
path_to_file : str
path to .smi file
kekulize : bool
kekulize or not
add_Hs : bool
add implicit hydrogens to the molecule or not.
all_single : bool
if True, all multiple bonds are summarized into a single bond with some attributes
Yields
------
Hypergraph
"""
def __init__(self, path_to_file, kekulize=True, add_Hs=False, all_single=True):
self.num_line = 1
self.mol_gen = Chem.SmilesMolSupplier(path_to_file, titleLine=False)
self.kekulize = kekulize
self.add_Hs = add_Hs
self.all_single = all_single
def __iter__(self):
return self
def __next__(self):
'''
each_mol = None
while each_mol is None:
each_mol = next(self.mol_gen)
'''
# not ignoring parse errors
each_mol = next(self.mol_gen)
if each_mol is None:
raise ValueError(f'incorrect smiles in line {self.num_line}')
else:
self.num_line += 1
return mol_to_hg(each_mol, self.kekulize, self.add_Hs)
def mol_to_bipartite(mol, kekulize):
"""
get a bipartite representation of a molecule.
Parameters
----------
mol : rdkit.Chem.rdchem.Mol
molecule object
Returns
-------
nx.Graph
a bipartite graph representing which bond is connected to which atoms.
"""
try:
mol = standardize_stereo(mol)
except KeyError:
print(Chem.MolToSmiles(mol))
raise KeyError
if kekulize:
Chem.Kekulize(mol)
bipartite_g = nx.Graph()
for each_atom in mol.GetAtoms():
bipartite_g.add_node(f"atom_{each_atom.GetIdx()}",
atom_attr=atom_attr(each_atom, kekulize))
for each_bond in mol.GetBonds():
bond_idx = each_bond.GetIdx()
bipartite_g.add_node(
f"bond_{bond_idx}",
bond_attr=bond_attr(each_bond, kekulize))
bipartite_g.add_edge(
f"atom_{each_bond.GetBeginAtomIdx()}",
f"bond_{bond_idx}")
bipartite_g.add_edge(
f"atom_{each_bond.GetEndAtomIdx()}",
f"bond_{bond_idx}")
return bipartite_g
def mol_to_hg(mol, kekulize, add_Hs):
"""
get a bipartite representation of a molecule.
Parameters
----------
mol : rdkit.Chem.rdchem.Mol
molecule object
kekulize : bool
kekulize or not
add_Hs : bool
add implicit hydrogens to the molecule or not.
Returns
-------
Hypergraph
"""
if add_Hs:
mol = Chem.AddHs(mol)
if kekulize:
Chem.Kekulize(mol)
bipartite_g = mol_to_bipartite(mol, kekulize)
hg = Hypergraph()
for each_atom in [each_node for each_node in bipartite_g.nodes()
if each_node.startswith('atom_')]:
node_set = set([])
for each_bond in bipartite_g.adj[each_atom]:
hg.add_node(each_bond,
attr_dict=bipartite_g.nodes[each_bond]['bond_attr'])
node_set.add(each_bond)
hg.add_edge(node_set,
attr_dict=bipartite_g.nodes[each_atom]['atom_attr'])
return hg
def hg_to_mol(hg, verbose=False):
""" convert a hypergraph into Mol object
Parameters
----------
hg : Hypergraph
Returns
-------
mol : Chem.RWMol
"""
mol = Chem.RWMol()
atom_dict = {}
bond_set = set([])
for each_edge in hg.edges:
atom = Chem.Atom(hg.edge_attr(each_edge)['symbol'].symbol)
atom.SetNumExplicitHs(hg.edge_attr(each_edge)['symbol'].num_explicit_Hs)
atom.SetFormalCharge(hg.edge_attr(each_edge)['symbol'].formal_charge)
atom.SetChiralTag(
Chem.rdchem.ChiralType.values[
hg.edge_attr(each_edge)['symbol'].chirality])
atom_idx = mol.AddAtom(atom)
atom_dict[each_edge] = atom_idx
for each_node in hg.nodes:
edge_1, edge_2 = hg.adj_edges(each_node)
if edge_1+edge_2 not in bond_set:
if hg.node_attr(each_node)['symbol'].bond_type <= 3:
num_bond = hg.node_attr(each_node)['symbol'].bond_type
elif hg.node_attr(each_node)['symbol'].bond_type == 12:
num_bond = 1
else:
raise ValueError(f'too many bonds; {hg.node_attr(each_node)["bond_symbol"].bond_type}')
_ = mol.AddBond(atom_dict[edge_1],
atom_dict[edge_2],
order=Chem.rdchem.BondType.values[num_bond])
bond_idx = mol.GetBondBetweenAtoms(atom_dict[edge_1], atom_dict[edge_2]).GetIdx()
# stereo
mol.GetBondWithIdx(bond_idx).SetStereo(
Chem.rdchem.BondStereo.values[hg.node_attr(each_node)['symbol'].stereo])
bond_set.update([edge_1+edge_2])
bond_set.update([edge_2+edge_1])
mol.UpdatePropertyCache()
mol = mol.GetMol()
not_stereo_mol = deepcopy(mol)
if Chem.MolFromSmiles(Chem.MolToSmiles(not_stereo_mol)) is None:
raise RuntimeError('no valid molecule was obtained.')
try:
mol = set_stereo(mol)
is_stereo = True
except:
import traceback
traceback.print_exc()
is_stereo = False
mol_tmp = deepcopy(mol)
Chem.SetAromaticity(mol_tmp)
if Chem.MolFromSmiles(Chem.MolToSmiles(mol_tmp)) is not None:
mol = mol_tmp
else:
if Chem.MolFromSmiles(Chem.MolToSmiles(mol)) is None:
mol = not_stereo_mol
mol.UpdatePropertyCache()
Chem.GetSymmSSSR(mol)
mol = Chem.MolFromSmiles(Chem.MolToSmiles(mol))
if verbose:
return mol, is_stereo
else:
return mol
def hgs_to_mols(hg_list, ignore_error=False):
if ignore_error:
mol_list = []
for each_hg in hg_list:
try:
mol = hg_to_mol(each_hg)
except:
mol = None
mol_list.append(mol)
else:
mol_list = [hg_to_mol(each_hg) for each_hg in hg_list]
return mol_list
def hgs_to_smiles(hg_list, ignore_error=False):
mol_list = hgs_to_mols(hg_list, ignore_error)
smiles_list = []
for each_mol in mol_list:
try:
smiles_list.append(
Chem.MolToSmiles(
Chem.MolFromSmiles(
Chem.MolToSmiles(
each_mol))))
except:
smiles_list.append(None)
return smiles_list
def atom_attr(atom, kekulize):
"""
get atom's attributes
Parameters
----------
atom : rdkit.Chem.rdchem.Atom
kekulize : bool
kekulize or not
Returns
-------
atom_attr : dict
"is_aromatic" : bool
the atom is aromatic or not.
"smarts" : str
SMARTS representation of the atom.
"""
if kekulize:
return {'terminal': True,
'is_in_ring': atom.IsInRing(),
'symbol': TSymbol(degree=0,
#degree=atom.GetTotalDegree(),
is_aromatic=False,
symbol=atom.GetSymbol(),
num_explicit_Hs=atom.GetNumExplicitHs(),
formal_charge=atom.GetFormalCharge(),
chirality=atom.GetChiralTag().real
)}
else:
return {'terminal': True,
'is_in_ring': atom.IsInRing(),
'symbol': TSymbol(degree=0,
#degree=atom.GetTotalDegree(),
is_aromatic=atom.GetIsAromatic(),
symbol=atom.GetSymbol(),
num_explicit_Hs=atom.GetNumExplicitHs(),
formal_charge=atom.GetFormalCharge(),
chirality=atom.GetChiralTag().real
)}
def bond_attr(bond, kekulize):
"""
get atom's attributes
Parameters
----------
bond : rdkit.Chem.rdchem.Bond
kekulize : bool
kekulize or not
Returns
-------
bond_attr : dict
"bond_type" : int
{0: rdkit.Chem.rdchem.BondType.UNSPECIFIED,
1: rdkit.Chem.rdchem.BondType.SINGLE,
2: rdkit.Chem.rdchem.BondType.DOUBLE,
3: rdkit.Chem.rdchem.BondType.TRIPLE,
4: rdkit.Chem.rdchem.BondType.QUADRUPLE,
5: rdkit.Chem.rdchem.BondType.QUINTUPLE,
6: rdkit.Chem.rdchem.BondType.HEXTUPLE,
7: rdkit.Chem.rdchem.BondType.ONEANDAHALF,
8: rdkit.Chem.rdchem.BondType.TWOANDAHALF,
9: rdkit.Chem.rdchem.BondType.THREEANDAHALF,
10: rdkit.Chem.rdchem.BondType.FOURANDAHALF,
11: rdkit.Chem.rdchem.BondType.FIVEANDAHALF,
12: rdkit.Chem.rdchem.BondType.AROMATIC,
13: rdkit.Chem.rdchem.BondType.IONIC,
14: rdkit.Chem.rdchem.BondType.HYDROGEN,
15: rdkit.Chem.rdchem.BondType.THREECENTER,
16: rdkit.Chem.rdchem.BondType.DATIVEONE,
17: rdkit.Chem.rdchem.BondType.DATIVE,
18: rdkit.Chem.rdchem.BondType.DATIVEL,
19: rdkit.Chem.rdchem.BondType.DATIVER,
20: rdkit.Chem.rdchem.BondType.OTHER,
21: rdkit.Chem.rdchem.BondType.ZERO}
"""
if kekulize:
is_aromatic = False
if bond.GetBondType().real == 12:
bond_type = 1
else:
bond_type = bond.GetBondType().real
else:
is_aromatic = bond.GetIsAromatic()
bond_type = bond.GetBondType().real
return {'symbol': BondSymbol(is_aromatic=is_aromatic,
bond_type=bond_type,
stereo=int(bond.GetStereo())),
'is_in_ring': bond.IsInRing()}
def standardize_stereo(mol):
'''
0: rdkit.Chem.rdchem.BondDir.NONE,
1: rdkit.Chem.rdchem.BondDir.BEGINWEDGE,
2: rdkit.Chem.rdchem.BondDir.BEGINDASH,
3: rdkit.Chem.rdchem.BondDir.ENDDOWNRIGHT,
4: rdkit.Chem.rdchem.BondDir.ENDUPRIGHT,
'''
# mol = Chem.AddHs(mol) # this removes CIPRank !!!
for each_bond in mol.GetBonds():
if int(each_bond.GetStereo()) in [2, 3]: #2=Z (same side), 3=E
begin_stereo_atom_idx = each_bond.GetBeginAtomIdx()
end_stereo_atom_idx = each_bond.GetEndAtomIdx()
atom_idx_1 = each_bond.GetStereoAtoms()[0]
atom_idx_2 = each_bond.GetStereoAtoms()[1]
if mol.GetBondBetweenAtoms(atom_idx_1, begin_stereo_atom_idx):
begin_atom_idx = atom_idx_1
end_atom_idx = atom_idx_2
else:
begin_atom_idx = atom_idx_2
end_atom_idx = atom_idx_1
begin_another_atom_idx = None
assert len(mol.GetAtomWithIdx(begin_stereo_atom_idx).GetNeighbors()) <= 3
for each_neighbor in mol.GetAtomWithIdx(begin_stereo_atom_idx).GetNeighbors():
each_neighbor_idx = each_neighbor.GetIdx()
if each_neighbor_idx not in [end_stereo_atom_idx, begin_atom_idx]:
begin_another_atom_idx = each_neighbor_idx
end_another_atom_idx = None
assert len(mol.GetAtomWithIdx(end_stereo_atom_idx).GetNeighbors()) <= 3
for each_neighbor in mol.GetAtomWithIdx(end_stereo_atom_idx).GetNeighbors():
each_neighbor_idx = each_neighbor.GetIdx()
if each_neighbor_idx not in [begin_stereo_atom_idx, end_atom_idx]:
end_another_atom_idx = each_neighbor_idx
'''
relationship between begin_atom_idx and end_atom_idx is encoded in GetStereo
'''
begin_atom_rank = int(mol.GetAtomWithIdx(begin_atom_idx).GetProp('_CIPRank'))
end_atom_rank = int(mol.GetAtomWithIdx(end_atom_idx).GetProp('_CIPRank'))
try:
begin_another_atom_rank = int(mol.GetAtomWithIdx(begin_another_atom_idx).GetProp('_CIPRank'))
except:
begin_another_atom_rank = np.inf
try:
end_another_atom_rank = int(mol.GetAtomWithIdx(end_another_atom_idx).GetProp('_CIPRank'))
except:
end_another_atom_rank = np.inf
if begin_atom_rank < begin_another_atom_rank\
and end_atom_rank < end_another_atom_rank:
pass
elif begin_atom_rank < begin_another_atom_rank\
and end_atom_rank > end_another_atom_rank:
# (begin_atom_idx +) end_another_atom_idx should be in StereoAtoms
if each_bond.GetStereo() == 2:
# set stereo
each_bond.SetStereo(Chem.rdchem.BondStereo.values[3])
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 3)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 3)
elif each_bond.GetStereo() == 3:
# set stereo
each_bond.SetStereo(Chem.rdchem.BondStereo.values[2])
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 3)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 4)
else:
raise ValueError
each_bond.SetStereoAtoms(begin_atom_idx, end_another_atom_idx)
elif begin_atom_rank > begin_another_atom_rank\
and end_atom_rank < end_another_atom_rank:
# (end_atom_idx +) begin_another_atom_idx should be in StereoAtoms
if each_bond.GetStereo() == 2:
# set stereo
each_bond.SetStereo(Chem.rdchem.BondStereo.values[3])
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 4)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 4)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 0)
elif each_bond.GetStereo() == 3:
# set stereo
each_bond.SetStereo(Chem.rdchem.BondStereo.values[2])
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 4)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 3)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 0)
else:
raise ValueError
each_bond.SetStereoAtoms(begin_another_atom_idx, end_atom_idx)
elif begin_atom_rank > begin_another_atom_rank\
and end_atom_rank > end_another_atom_rank:
# begin_another_atom_idx + end_another_atom_idx should be in StereoAtoms
if each_bond.GetStereo() == 2:
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 4)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 3)
elif each_bond.GetStereo() == 3:
# set bond dir
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, begin_another_atom_idx, begin_stereo_atom_idx, 4)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 0)
mol = safe_set_bond_dir(mol, end_another_atom_idx, end_stereo_atom_idx, 4)
else:
raise ValueError
each_bond.SetStereoAtoms(begin_another_atom_idx, end_another_atom_idx)
else:
raise RuntimeError
return mol
def set_stereo(mol):
'''
0: rdkit.Chem.rdchem.BondDir.NONE,
1: rdkit.Chem.rdchem.BondDir.BEGINWEDGE,
2: rdkit.Chem.rdchem.BondDir.BEGINDASH,
3: rdkit.Chem.rdchem.BondDir.ENDDOWNRIGHT,
4: rdkit.Chem.rdchem.BondDir.ENDUPRIGHT,
'''
_mol = Chem.MolFromSmiles(Chem.MolToSmiles(mol))
Chem.Kekulize(_mol, True)
substruct_match = mol.GetSubstructMatch(_mol)
if not substruct_match:
''' mol and _mol are kekulized.
sometimes, the order of '=' and '-' changes, which causes mol and _mol not matched.
'''
Chem.SetAromaticity(mol)
Chem.SetAromaticity(_mol)
substruct_match = mol.GetSubstructMatch(_mol)
try:
atom_match = {substruct_match[_mol_atom_idx]: _mol_atom_idx for _mol_atom_idx in range(_mol.GetNumAtoms())} # mol to _mol
except:
raise ValueError('two molecules obtained from the same data do not match.')
for each_bond in mol.GetBonds():
begin_atom_idx = each_bond.GetBeginAtomIdx()
end_atom_idx = each_bond.GetEndAtomIdx()
_bond = _mol.GetBondBetweenAtoms(atom_match[begin_atom_idx], atom_match[end_atom_idx])
_bond.SetStereo(each_bond.GetStereo())
mol = _mol
for each_bond in mol.GetBonds():
if int(each_bond.GetStereo()) in [2, 3]: #2=Z (same side), 3=E
begin_stereo_atom_idx = each_bond.GetBeginAtomIdx()
end_stereo_atom_idx = each_bond.GetEndAtomIdx()
begin_atom_idx_set = set([each_neighbor.GetIdx()
for each_neighbor
in mol.GetAtomWithIdx(begin_stereo_atom_idx).GetNeighbors()
if each_neighbor.GetIdx() != end_stereo_atom_idx])
end_atom_idx_set = set([each_neighbor.GetIdx()
for each_neighbor
in mol.GetAtomWithIdx(end_stereo_atom_idx).GetNeighbors()
if each_neighbor.GetIdx() != begin_stereo_atom_idx])
if not begin_atom_idx_set:
each_bond.SetStereo(Chem.rdchem.BondStereo(0))
continue
if not end_atom_idx_set:
each_bond.SetStereo(Chem.rdchem.BondStereo(0))
continue
if len(begin_atom_idx_set) == 1:
begin_atom_idx = begin_atom_idx_set.pop()
begin_another_atom_idx = None
if len(end_atom_idx_set) == 1:
end_atom_idx = end_atom_idx_set.pop()
end_another_atom_idx = None
if len(begin_atom_idx_set) == 2:
atom_idx_1 = begin_atom_idx_set.pop()
atom_idx_2 = begin_atom_idx_set.pop()
if int(mol.GetAtomWithIdx(atom_idx_1).GetProp('_CIPRank')) < int(mol.GetAtomWithIdx(atom_idx_2).GetProp('_CIPRank')):
begin_atom_idx = atom_idx_1
begin_another_atom_idx = atom_idx_2
else:
begin_atom_idx = atom_idx_2
begin_another_atom_idx = atom_idx_1
if len(end_atom_idx_set) == 2:
atom_idx_1 = end_atom_idx_set.pop()
atom_idx_2 = end_atom_idx_set.pop()
if int(mol.GetAtomWithIdx(atom_idx_1).GetProp('_CIPRank')) < int(mol.GetAtomWithIdx(atom_idx_2).GetProp('_CIPRank')):
end_atom_idx = atom_idx_1
end_another_atom_idx = atom_idx_2
else:
end_atom_idx = atom_idx_2
end_another_atom_idx = atom_idx_1
if each_bond.GetStereo() == 2: # same side
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 3)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 4)
each_bond.SetStereoAtoms(begin_atom_idx, end_atom_idx)
elif each_bond.GetStereo() == 3: # opposite side
mol = safe_set_bond_dir(mol, begin_atom_idx, begin_stereo_atom_idx, 3)
mol = safe_set_bond_dir(mol, end_atom_idx, end_stereo_atom_idx, 3)
each_bond.SetStereoAtoms(begin_atom_idx, end_atom_idx)
else:
raise ValueError
return mol
def safe_set_bond_dir(mol, atom_idx_1, atom_idx_2, bond_dir_val):
if atom_idx_1 is None or atom_idx_2 is None:
return mol
else:
mol.GetBondBetweenAtoms(atom_idx_1, atom_idx_2).SetBondDir(Chem.rdchem.BondDir.values[bond_dir_val])
return mol