def tet_fix_stereo(smiles, frag):
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f._find_stereo()
frag = chemi.smiles_to_oemol(frag, add_atom_map=True)
fixed = f._fix_stereo(frag)
assert f._check_stereo(fixed) == True
def test_stereo_parent(self):
"""Test non isomeric and isomeric parent molecule SMILES"""
smiles = 'NC(C)(F)C(=O)O'
isomeric_smiles_r = 'N[C@](C)(F)C(=O)O'
isomeric_smiles_s = 'N[C@@](C)(F)C(=O)O'
mol_1 = chemi.smiles_to_oemol(smiles)
mol_2 = chemi.smiles_to_oemol(isomeric_smiles_r)
mol_3 = chemi.smiles_to_oemol(isomeric_smiles_s)
self.assertFalse(fragmenter.fragment._generate_fragments(mol_1))
fragmenter.fragment._generate_fragments(mol_1, strict_stereo=False)
fragmenter.fragment._generate_fragments(mol_2)
fragmenter.fragment._generate_fragments(mol_3)
def test_smiles_to_oemol():
from openeye import oechem
mol = chemi.smiles_to_oemol('CCCC')
assert isinstance(mol, oechem.OEMol)
assert oechem.OEMolToSmiles(mol) == 'CCCC'
assert mol.GetTitle() == 'butane'
mol = chemi.smiles_to_oemol('CCCC', normalize=False)
assert mol.GetTitle() == ''
mol = chemi.smiles_to_oemol('CCCC', add_atom_map=True)
assert oechem.OEMolToSmiles(
mol
) == '[H:5][C:1]([H:6])([H:7])[C:3]([H:11])([H:12])[C:4]([H:13])([H:14])[C:2]([H:8])([H:9])[H:10]'
def test_formal_charge(self):
"""Test formal charge"""
mol_1 = chemi.smiles_to_oemol('c1cc(c[nH+]c1)c2ccncn2')
charge = chemi.get_charge(mol_1)
self.assertEqual(charge, 1)
mol_2 = chemi.smiles_to_oemol('C[NH+]1CC[NH+](CC1)Cc2ccccc2')
charge = chemi.get_charge(mol_2)
self.assertEqual(charge, 2)
mol_3 = chemi.smiles_to_oemol('CCC(C)(C)C(=O)[O-]')
charge = chemi.get_charge(mol_3)
self.assertEqual(charge, -1)
def test_expand_protonation_states(self):
"""Test expand protonation states"""
smiles = 'C5=C(C1=CN=CC=C1)N=C(NC2=C(C=CC(=C2)NC(C3=CC=C(C=C3)CN4CCN(CC4)C)=O)C)N=C5'
molecule = chemi.smiles_to_oemol(smiles)
protonation = fragmenter.fragment._expand_states(molecule)
protonation_1 = {
'Cc1ccc(cc1Nc2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)CN5CCN(CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)CN5CC[NH+](CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)C[NH+]5CCN(CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)C[NH+]5CC[NH+](CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)CN5CCN(CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)CN5CC[NH+](CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)C[NH+]5CCN(CC5)C',
'Cc1ccc(cc1Nc2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)C[NH+]5CC[NH+](CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)CN5CCN(CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)CN5CC[NH+](CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)C[NH+]5CCN(CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3ccc[nH+]c3)NC(=O)c4ccc(cc4)C[NH+]5CC[NH+](CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)CN5CCN(CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)CN5CC[NH+](CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)C[NH+]5CCN(CC5)C',
'Cc1ccc(cc1[N-]c2nccc(n2)c3cccnc3)NC(=O)c4ccc(cc4)C[NH+]5CC[NH+](CC5)C'
}
protonation_2 = set()
for mol in protonation:
protonation_2.add(
mol_to_smiles(mol,
mapped=False,
explicit_hydrogen=False,
isomeric=True))
intersection = protonation_1.intersection(protonation_2)
self.assertEqual(len(intersection), len(protonation_1))
self.assertEqual(len(intersection), len(protonation_2))
def test_expand_tautomers(self):
"""Test expand tautomer"""
smiles_1 = 'c1ccc2c(c1)C=CCC2=O'
smiles_2 = 'c1ccc2c(c1)cccc2O'
molecule_1 = chemi.smiles_to_oemol(smiles_1)
molecule_2 = chemi.smiles_to_oemol(smiles_2)
tautomers_1 = fragmenter.fragment.expand_states(molecule_1,
protonation=False,
tautomers=True,
stereoisomers=False)
tautomers_2 = fragmenter.fragment.expand_states(molecule_2,
protonation=False,
tautomers=True,
stereoisomers=False)
self.assertEqual(tautomers_1, tautomers_2)
def test_generate_conformers():
mol = chemi.smiles_to_oemol('CCCCCCC')
confs = chemi.generate_conformers(mol, max_confs=1)
assert confs.GetMaxConfIdx() == 1
confs = chemi.generate_conformers(mol)
assert confs.GetMaxConfIdx() == 3
def test_add_substituent():
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
assert mol_to_smiles(f.fragments[(3, 5)],
mapped=False,
explicit_hydrogen=False) == 'CCCCC'
mol = f.fragments[(3, 5)]
atoms = set()
bonds = set()
for a in mol.GetAtoms():
if a.IsHydrogen():
continue
atoms.add(a.GetMapIdx())
for b in mol.GetBonds():
a1 = b.GetBgn()
a2 = b.GetEnd()
if a1.IsHydrogen() or a2.IsHydrogen():
continue
bonds.add((a1.GetMapIdx(), a2.GetMapIdx()))
mol = f._add_next_substituent(atoms, bonds, target_bond=(3, 5))
assert mol_to_smiles(mol, mapped=False,
explicit_hydrogen=False) == 'CCCCCC'
def test_to_qcschema_mols():
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
qcschema_mol = f.to_qcschema_mols()
assert len(qcschema_mol) == 2
def test_depict_fragments(engine):
mol = chemi.smiles_to_oemol('CCCCC')
if engine == 'WBO':
f = fragmenter.fragment.WBOFragmenter(mol)
if engine =='combinatorial':
f = fragmenter.fragment.CombinatorialFragmenter(mol)
f.fragment()
assert f.depict_fragments('test.pdf') == True
def test_td_inputs():
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
td_inputs = f.to_torsiondrive_json()
assert len(td_inputs) == 2
def test_get_ring_and_fgroup(input, bond, output):
mol = chemi.smiles_to_oemol(input)
f = fragmenter.fragment.PfizerFragmenter(mol)
atoms, bonds = f._get_torsion_quartet(bond)
l_atoms = len(atoms)
l_bonds = len(bonds)
atoms_2, bonds_2 = f._get_ring_and_fgroups(atoms, bonds)
assert (l_atoms == len(atoms_2)) == output
assert (l_bonds == len(bonds_2)) == output
def generate_grid_conformers():
mol = chemi.smiles_to_oemol('CCCC')
dihedrals = [(0, 2, 3, 1), (3, 2, 0, 4)]
intervals = [30, 90]
grid = chemi.generate_grid_conformers(mol,
dihedrals=dihedrals,
intervals=intervals)
assert grid.GetMaxConfIdx() == 48
def test_cap_open_valance(input, bond, output):
from openeye import oechem
mol = chemi.smiles_to_oemol(input)
f = fragmenter.fragment.PfizerFragmenter(mol)
atoms, bonds = f._get_torsion_quartet(bond)
atoms, bonds = f._get_ring_and_fgroups(atoms, bonds)
f._cap_open_valence(atoms, bonds, bond)
# Check that carbon bonded to N was added
assert f.molecule.GetAtom(oechem.OEHasMapIdx(output))
def test_to_json():
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
json_dict = f.to_json()
assert len(json_dict) == 2
assert list(json_dict.keys())[0] == 'CCCCC'
assert 'provenance' in json_dict['CCCCC']
assert 'cmiles_identifiers' in json_dict['CCCCC']
def test_get_charges(keep_confs, output):
mol = chemi.smiles_to_oemol('CCCCCCC')
if output == 'error':
with pytest.raises(ValueError):
chemi.get_charges(mol, keep_confs=keep_confs)
else:
charged = chemi.get_charges(mol, keep_confs=keep_confs)
for i, c in enumerate(charged.GetConfs()):
i += 1
assert i == output
def test_build_WBOfragment():
""" Test build fragment"""
from openeye import oechem
smiles = 'CCCCC'
mol = chemi.smiles_to_oemol(smiles)
oechem.OESmilesToMol(mol, smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
assert len(f.fragments) == len(f.rotors_wbo)
assert f.fragments.keys() == f.rotors_wbo.keys()
def test_2D_conformation(self):
"""Test checking for 2D conformation"""
from fragmenter import chemi, states
mol = chemi.smiles_to_oemol('CCCC')
states = states.enumerate_states(mol, return_mols=True)
for state in states:
self.assertFalse(chemi.has_conformer(state, check_two_dimension=True))
conf = chemi.generate_conformers(mol, max_confs=1)
self.assertTrue(chemi.has_conformer(conf, check_two_dimension=True))
def test_has_conformer(self):
"""Test has conformer"""
infile = get_fn('butane.pdb')
ifs = oechem.oemolistream(infile)
molecule_with_conf = oechem.OEMol()
oechem.OEReadMolecule(ifs, molecule_with_conf)
self.assertTrue(chemi.has_conformer(molecule_with_conf))
molecule_without_conf = chemi.smiles_to_oemol('CCCC')
self.assertFalse(chemi.has_conformer(molecule_without_conf))
def test_atom_map_order(self):
"""Test atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_from_tagged_smiles = chemi.smiles_to_oemol(tagged_smiles)
atom_map = get_atom_map(mol_from_tagged_smiles, tagged_smiles)
# Compare atom map to tag
for i in range(1, len(atom_map) + 1):
atom_1 = mol_from_tagged_smiles.GetAtom(
oechem.OEHasAtomIdx(atom_map[i]))
self.assertEqual(i, atom_1.GetMapIdx())
def test_calculate_wbo():
smiles = 'CCCC'
oemol = chemi.smiles_to_oemol(smiles, name='butane')
f = fragmenter.fragment.WBOFragmenter(oemol)
mol = f.calculate_wbo()
assert not mol
for bond in f.molecule.GetBonds():
assert 'WibergBondOrder' in bond.GetData()
mol = f.calculate_wbo(f.molecule)
assert mol
for bond in mol.GetBonds():
assert 'WibergBondOrder' in bond.GetData()
def test_to_qcscheme_mol():
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.fragment()
qcschema_mol = f._to_qcschema_mol(f.fragments[(3, 5)])
assert 'initial_molecule' in qcschema_mol
assert 'geometry' in qcschema_mol['initial_molecule'][0]
assert 'symbols' in qcschema_mol['initial_molecule'][0]
assert 'connectivity' in qcschema_mol['initial_molecule'][0]
assert 'identifiers' in qcschema_mol
assert 'provenance' in qcschema_mol
def test_build_fragment():
from openeye import oechem
smiles = 'CCCCCC'
mol = chemi.smiles_to_oemol(smiles)
f = fragmenter.fragment.WBOFragmenter(mol)
f.calculate_wbo()
f._get_rotor_wbo()
setattr(f, 'threshold', 0.05)
for bond in f.rotors_wbo:
f._build_fragment(bond)
assert len(f.fragments) == 3
for bond in f.fragments:
remove_atom_map(f.fragments[bond])
assert oechem.OEMolToSmiles(f.fragments[bond]) == 'CCCC'
def test_atom_map(self):
"""Test get atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_1 = chemi.smiles_to_oemol('CC[N+]#C')
inf = get_fn('ethylmethylidyneamonium.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = get_atom_map(mol_1, tagged_smiles)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1),
oechem.OECreateCanSmiString(mol_2))
# Test aromatic molecule
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = chemi.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = get_atom_map(mol_1, tagged_smiles)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1),
oechem.OECreateCanSmiString(mol_2))
def test_mapped_xyz(self):
"""Test writing out mapped xyz"""
from openeye import oechem, oeomega
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = chemi.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
mol_1 = chemi.generate_conformers(mol_1, max_confs=1)
atom_map = get_atom_map(mol_1, tagged_smiles)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
xyz_1 = chemi.to_mapped_xyz(mol_1, atom_map, xyz_format=False)
# molecule generated from mol2 should be in the right order.
atom_map_mol2 = {
1: 0,
2: 1,
3: 2,
4: 3,
5: 4,
6: 5,
7: 6,
8: 7,
9: 8,
10: 9,
11: 10,
12: 11,
13: 12,
14: 13,
15: 14
}
xyz_2 = chemi.to_mapped_xyz(mol_2, atom_map_mol2, xyz_format=False)
for ele1, ele2 in zip(xyz_1.split('\n')[:-1], xyz_2.split('\n')[:-1]):
self.assertEqual(ele1.split(' ')[2], ele2.split(' ')[2])
def enumerate_fragments(molecule,
title='',
mol_provenance=None,
json_filename=None,
generate_vis=True):
"""
Fragment molecule
Parameters
----------
molecule: Input molecule. Very permissive. Can be anything that OpenEye can parse
SMILES string of molecule to fragment
title: str, optional. Default empty str
The title or name of the molecule. If empty stirng will use the IUPAC name for molecule title.
mol_provenance: dict, optional. Default is None
provenance for molecule. If the molecule is a state from enumerate_states, the provenance from enumerate_states
should be used
json_filename: str, optional. Default None
If a filename is provided, will write output to json file.
generate_vis: bool, optional, default False
If True, will generate visualization of fragments from parent molecule
"""
parent_molecule = chemi.smiles_to_oemol(molecule, name=title)
fragment_engine = fragment.CombinatorialFragmenter(parent_molecule,
functional_groups=False)
fragment_engine.fragment()
frag_json = fragment_engine.to_json()
with open(json_filename, 'w') as f:
json.dump(frag_json, f, indent=2, sort_keys=True)
if len(fragment_engine.new_stereo) > 0:
# Save fragments that are missing stereo because of new stereo center
chemi.smiles_to_smi(fragment_engine.new_stereo,
filename='{}_new_stereo_missing.smi'.format(title))
if generate_vis:
fname = '{}.pdf'.format(parent_molecule.GetTitle())
fragment_engine.depict_fragments(fname=fname)
def test_expand_enantiomers(self):
smiles = 'CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4'
molecule = chemi.smiles_to_oemol(smiles)
stereoisomers = fragmenter.fragment._expand_states(
molecule, enumerate='stereoisomers')
stereoisomers_1 = {
'CN(C)C/C=C/C(=O)Nc1cc2c(cc1O[C@@H]3CCOC3)ncnc2Nc4ccc(c(c4)Cl)F',
'CN(C)C/C=C/C(=O)Nc1cc2c(cc1O[C@H]3CCOC3)ncnc2Nc4ccc(c(c4)Cl)F',
'CN(C)C/C=C\\C(=O)Nc1cc2c(cc1O[C@@H]3CCOC3)ncnc2Nc4ccc(c(c4)Cl)F',
'CN(C)C/C=C\\C(=O)Nc1cc2c(cc1O[C@H]3CCOC3)ncnc2Nc4ccc(c(c4)Cl)F'
}
stereoisomers_2 = set()
for mol in stereoisomers:
stereoisomers_2.add(
mol_to_smiles(mol,
mapped=False,
explicit_hydrogen=False,
isomeric=True))
intersection = stereoisomers_1.intersection(stereoisomers_2)
self.assertEqual(len(intersection), len(stereoisomers_1))
self.assertEqual(len(intersection), len(stereoisomers_2))
self.assertEqual(len(stereoisomers_1), len(stereoisomers_2))
def test_find_torsion_around_bond():
mol = chemi.smiles_to_oemol('CCCC', add_atom_map=True)
dihedral = torsions.find_torsion_around_bond(mol, (3, 4))
assert dihedral == [0, 2, 3, 1]
def mapped_molecule():
return chemi.smiles_to_oemol(
'[H:5][C:1]([H:6])([H:7])[C:3]([H:11])([H:12])[C:4]([H:13])([H:14])[C:2]([H:8])([H:9])[H:10]'
)
def test_pfizer_fragmenter(input, output):
mol = chemi.smiles_to_oemol(input)
f = fragmenter.fragment.PfizerFragmenter(mol)
f.fragment()
assert len(f.fragments) == output