def edit_mol(rmol, edits, tatoms):
new_mol = Chem.RWMol(rmol)
[a.SetNumExplicitHs(0) for a in new_mol.GetAtoms()]
amap = {}
for atom in rmol.GetAtoms():
amap[atom.GetAtomMapNum() - 1] = atom.GetIdx()
for x, y, t, v in edits:
bond = new_mol.GetBondBetweenAtoms(amap[x], amap[y])
# a1 = new_mol.GetAtomWithIdx(amap[x])
# a2 = new_mol.GetAtomWithIdx(amap[y])
if bond is not None:
new_mol.RemoveBond(amap[x], amap[y])
if t > 0:
new_mol.AddBond(amap[x], amap[y], BOND_FLOAT_TO_TYPE[t])
pred_mol = new_mol.GetMol()
pred_smiles = Chem.MolToSmiles(pred_mol)
pred_list = pred_smiles.split('.')
pred_mols = []
for pred_smiles in pred_list:
mol = Chem.MolFromSmiles(pred_smiles)
if mol is None: continue
atom_set = set([atom.GetAtomMapNum() - 1 for atom in mol.GetAtoms()])
if len(atom_set & tatoms) == 0:
continue
for atom in mol.GetAtoms():
atom.SetAtomMapNum(0)
pred_mols.append(mol)
return '.'.join(
sorted([Chem.MolToSmiles(pred_mol) for pred_mol in pred_mols]))
def __init__(self, smiles=None, rdk=None, conv_enabled=False):
"""Constructor
Keyword Arguments:
smiles {str} -- SMILES representation of a molecule (default: {None})
rdk {rdkit Mol} -- molecule as an RDKit object (default: {None})
conv_enabled {bool} -- whether to set both smiles and graph
arguments here or lazily defer until called
(default: {False})
Raises:
ValueError -- if neither a correct smiles string
or a rdkit mol are provided
"""
if conv_enabled:
if isinstance(smiles, str):
# also checks if smiles can be parsed
rdk = Chem.MolFromSmiles(smiles)
assert rdk is not None
elif rdk is not None:
smiles = Chem.MolToSmiles(rdk)
else:
raise ValueError("Invalid arguments")
self.smiles = smiles
self.rdk = rdk
self.graph = None # should be obtained from rdk when needed
self.synthesis_path = [] # list of Reactions
self.begin_flag = True
def processMols(mols):
print('smiles\tName\tsa_score')
for i, m in enumerate(mols):
if m is None:
continue
s = calculateScore(m)
smiles = Chem.MolToSmiles(m)
print(smiles + "\t" + m.GetProp('_Name') + "\t%3f" % s)
def sanitize_smiles(smi, largest_fragment=False):
mol = Chem.MolFromSmiles(smi)
if mol is None:
return smi
try:
mol = standardizer.standardize(
mol) # standardize functional group reps
if largest_fragment:
mol = standardizer.largest_fragment(
mol) # remove product counterions/salts/etc.
mol = standardizer.uncharge(
mol) # neutralize, e.g., carboxylic acids
except Exception:
pass
return Chem.MolToSmiles(mol)
def to_smiles(self):
smiles = self.smiles
if self.smiles is None:
self.smiles = Chem.MolToSmiles(self.rdk)
return self.smiles
def edit_mol(rmol, edits):
new_mol = Chem.RWMol(rmol)
# Keep track of aromatic nitrogens, might cause explicit hydrogen issues
aromatic_nitrogen_idx = set()
aromatic_carbonyl_adj_to_aromatic_nH = {}
aromatic_carbondeg3_adj_to_aromatic_nH0 = {}
for a in new_mol.GetAtoms():
if a.GetIsAromatic() and a.GetSymbol() == 'N':
aromatic_nitrogen_idx.add(a.GetIdx())
for nbr in a.GetNeighbors():
if a.GetNumExplicitHs() == 1 and nbr.GetSymbol(
) == 'C' and nbr.GetIsAromatic() and any(
b.GetBondTypeAsDouble() == 2 for b in nbr.GetBonds()):
aromatic_carbonyl_adj_to_aromatic_nH[
nbr.GetIdx()] = a.GetIdx()
elif a.GetNumExplicitHs() == 0 and nbr.GetSymbol(
) == 'C' and nbr.GetIsAromatic() and len(nbr.GetBonds()) == 3:
aromatic_carbondeg3_adj_to_aromatic_nH0[
nbr.GetIdx()] = a.GetIdx()
else:
a.SetNumExplicitHs(0)
new_mol.UpdatePropertyCache()
amap = {}
for atom in rmol.GetAtoms():
amap[atom.GetIntProp('molAtomMapNumber')] = atom.GetIdx()
# Apply the edits as predicted
for x, y, t in edits:
bond = new_mol.GetBondBetweenAtoms(amap[x], amap[y])
a1 = new_mol.GetAtomWithIdx(amap[x])
a2 = new_mol.GetAtomWithIdx(amap[y])
if bond is not None:
new_mol.RemoveBond(amap[x], amap[y])
# Are we losing a bond on an aromatic nitrogen?
if bond.GetBondTypeAsDouble() == 1.0:
if amap[x] in aromatic_nitrogen_idx:
if a1.GetTotalNumHs() == 0:
a1.SetNumExplicitHs(1)
elif a1.GetFormalCharge() == 1:
a1.SetFormalCharge(0)
elif amap[y] in aromatic_nitrogen_idx:
if a2.GetTotalNumHs() == 0:
a2.SetNumExplicitHs(1)
elif a2.GetFormalCharge() == 1:
a2.SetFormalCharge(0)
# Are we losing a c=O bond on an aromatic ring? If so, remove H from adjacent nH if appropriate
if bond.GetBondTypeAsDouble() == 2.0:
if amap[x] in aromatic_carbonyl_adj_to_aromatic_nH:
new_mol.GetAtomWithIdx(
aromatic_carbonyl_adj_to_aromatic_nH[
amap[x]]).SetNumExplicitHs(0)
elif amap[y] in aromatic_carbonyl_adj_to_aromatic_nH:
new_mol.GetAtomWithIdx(
aromatic_carbonyl_adj_to_aromatic_nH[
amap[y]]).SetNumExplicitHs(0)
if t > 0:
new_mol.AddBond(amap[x], amap[y], BOND_TYPE[t])
# Special alkylation case?
if t == 1:
if amap[x] in aromatic_nitrogen_idx:
if a1.GetTotalNumHs() == 1:
a1.SetNumExplicitHs(0)
else:
a1.SetFormalCharge(1)
elif amap[y] in aromatic_nitrogen_idx:
if a2.GetTotalNumHs() == 1:
a2.SetNumExplicitHs(0)
else:
a2.SetFormalCharge(1)
# Are we getting a c=O bond on an aromatic ring? If so, add H to adjacent nH0 if appropriate
if t == 2:
if amap[x] in aromatic_carbondeg3_adj_to_aromatic_nH0:
new_mol.GetAtomWithIdx(
aromatic_carbondeg3_adj_to_aromatic_nH0[
amap[x]]).SetNumExplicitHs(1)
elif amap[y] in aromatic_carbondeg3_adj_to_aromatic_nH0:
new_mol.GetAtomWithIdx(
aromatic_carbondeg3_adj_to_aromatic_nH0[
amap[y]]).SetNumExplicitHs(1)
# Tried:
# bonds_to_remove.sort(key=lambda x: x[0], reverse=True)
# for (idx, bond) in bonds_to_remove:
# start = bond.GetBeginAtomIdx()
# end = bond.GetEndAtomIdx()
# new_mol.RemoveBond(start, end)
# pred_mol = new_mol.GetMol()
pred_mol = new_mol.GetMol()
# Clear formal charges to make molecules valid
# Note: because S and P (among others) can change valence, be more flexible
for atom in pred_mol.GetAtoms():
atom.ClearProp('molAtomMapNumber')
if atom.GetSymbol() == 'N' and atom.GetFormalCharge(
) == 1: # exclude negatively-charged azide
bond_vals = sum(
[bond.GetBondTypeAsDouble() for bond in atom.GetBonds()])
if bond_vals <= 3:
atom.SetFormalCharge(0)
elif atom.GetSymbol() == 'N' and atom.GetFormalCharge(
) == -1: # handle negatively-charged azide addition
bond_vals = sum(
[bond.GetBondTypeAsDouble() for bond in atom.GetBonds()])
if bond_vals == 3 and any(
[nbr.GetSymbol() == 'N' for nbr in atom.GetNeighbors()]):
atom.SetFormalCharge(0)
elif atom.GetSymbol() == 'N':
bond_vals = sum(
[bond.GetBondTypeAsDouble() for bond in atom.GetBonds()])
if bond_vals == 4 and not atom.GetIsAromatic(
): # and atom.IsInRingSize(5)):
atom.SetFormalCharge(1)
elif atom.GetSymbol() == 'C' and atom.GetFormalCharge() != 0:
atom.SetFormalCharge(0)
elif atom.GetSymbol() == 'O' and atom.GetFormalCharge() != 0:
bond_vals = sum(
[bond.GetBondTypeAsDouble()
for bond in atom.GetBonds()]) + atom.GetNumExplicitHs()
if bond_vals == 2:
atom.SetFormalCharge(0)
elif atom.GetSymbol() in ['Cl', 'Br', 'I', 'F'
] and atom.GetFormalCharge() != 0:
bond_vals = sum(
[bond.GetBondTypeAsDouble() for bond in atom.GetBonds()])
if bond_vals == 1:
atom.SetFormalCharge(0)
elif atom.GetSymbol() == 'S' and atom.GetFormalCharge() != 0:
bond_vals = sum(
[bond.GetBondTypeAsDouble() for bond in atom.GetBonds()])
if bond_vals in [2, 4, 6]:
atom.SetFormalCharge(0)
elif atom.GetSymbol(
) == 'P': # quartenary phosphorous should be pos. charge with 0 H
bond_vals = [
bond.GetBondTypeAsDouble() for bond in atom.GetBonds()
]
if sum(bond_vals) == 4 and len(bond_vals) == 4:
atom.SetFormalCharge(1)
atom.SetNumExplicitHs(0)
elif sum(bond_vals) == 3 and len(
bond_vals) == 3: # make sure neutral
atom.SetFormalCharge(0)
elif atom.GetSymbol(
) == 'B': # quartenary boron should be neg. charge with 0 H
bond_vals = [
bond.GetBondTypeAsDouble() for bond in atom.GetBonds()
]
if sum(bond_vals) == 4 and len(bond_vals) == 4:
atom.SetFormalCharge(-1)
atom.SetNumExplicitHs(0)
elif atom.GetSymbol() in ['Mg', 'Zn']:
bond_vals = [
bond.GetBondTypeAsDouble() for bond in atom.GetBonds()
]
if sum(bond_vals) == 1 and len(bond_vals) == 1:
atom.SetFormalCharge(1)
elif atom.GetSymbol() == 'Si':
bond_vals = [
bond.GetBondTypeAsDouble() for bond in atom.GetBonds()
]
if sum(bond_vals) == len(bond_vals):
atom.SetNumExplicitHs(max(0, 4 - len(bond_vals)))
# Bounce to/from SMILES to try to sanitize
pred_smiles = Chem.MolToSmiles(pred_mol) # <--- TODO: error occurs here
pred_list = pred_smiles.split('.')
pred_mols = [Chem.MolFromSmiles(pred_smiles) for pred_smiles in pred_list]
for i, mol in enumerate(pred_mols):
# Check if we failed/succeeded in previous step
if mol is None:
logging.debug('##### Unparseable mol: {}'.format(pred_list[i]))
continue
# Else, try post-sanitiztion fixes in structure
mol = Chem.MolFromSmiles(Chem.MolToSmiles(mol))
if mol is None:
continue
for rxn in clean_rxns_postsani:
out = rxn.RunReactants((mol, ))
if out:
try:
Chem.SanitizeMol(out[0][0])
pred_mols[i] = Chem.MolFromSmiles(
Chem.MolToSmiles(out[0][0]))
except Exception as e:
print(e)
print('Could not sanitize postsani reaction product: {}'.
format(Chem.MolToSmiles(out[0][0])))
print('Original molecule was: {}'.format(
Chem.MolToSmiles(mol)))
pred_smiles = [
Chem.MolToSmiles(pred_mol) for pred_mol in pred_mols
if pred_mol is not None
]
return pred_smiles
thisrow.append(r)
thisrow.append(p)
# Save pbond information
pbonds = {}
for bond in pmol.GetBonds():
a1 = idxfunc(bond.GetBeginAtom())
a2 = idxfunc(bond.GetEndAtom())
t = bond_types.index(bond.GetBondType())
pbonds[(a1, a2)] = pbonds[(a2, a1)] = t + 1
for atom in pmol.GetAtoms():
atom.ClearProp('molAtomMapNumber')
psmiles = Chem.MolToSmiles(pmol)
psmiles_sani = set(sanitize_smiles(psmiles, True).split('.'))
psmiles = set(psmiles.split('.'))
thisrow.append('.'.join(psmiles))
thisrow.append('.'.join(psmiles_sani))
########### Use *true* edits to try to recover product
if opts.bonds_as_doubles:
cbonds = []
for gedit in gedits.split(';'):
x, y, t = gedit.split('-')
x, y, t = int(x), int(y), float(t)
cbonds.append((x, y, bond_types_as_double[t]))
else: