def run_transforms(rxn_file, data_file, smarts):
"""
Given a reaction and a file with SMILES and activity values, generate products and check whether products are in
the input
:param rxn_file: reaction file name
:param data_file: data file name
:param smarts: smarts that must be matched by input molecules
:return: list of output molecules
"""
if smarts:
smarts_mol = Chem.MolFromSmarts(smarts)
if smarts_mol is None:
print(f"Could not parse SMARTS {smarts}")
sys.exit(1)
rxn = AllChem.ReactionFromRxnFile(rxn_file)
reactant_template = Chem.Mol(rxn.GetReactantTemplate(0))
product_template = Chem.Mol(rxn.GetProductTemplate(0))
# In order to make the output easier to understand, we will align the molecules to the reaction
# The aligned structures will look funny unless we scale the reaction and product templates
scale_molecule(reactant_template)
scale_molecule(product_template)
# Clear the atom maps from the templates, may not be necessary, but can't hurt
clear_atom_maps(reactant_template)
clear_atom_maps(product_template)
# Read in the data
df = pd.read_csv(data_file)
# Create a list of input molecules
mol_list = [Chem.MolFromSmiles(x) for x in df.SMILES]
df["Mol"] = [remove_salts(x) for x in mol_list]
# Build a dictionary of the input SMILES
smiles_dict = build_smiles_dictionary(df)
output_list = []
used = set()
# Loop over the molecules, apply the reaction and check if the product SMILES is in smiles_dict
# If it is, we have a pair
for (mol, name, val) in df[["Mol", "Name", "Value"]].values:
if smarts and not mol.HasSubstructMatch(smarts_mol):
continue
prods = rxn.RunReactants([mol])
for prod in prods:
prod_mol = prod[0]
prod_smiles = Chem.MolToSmiles(prod_mol)
prod_lookup = smiles_dict.get(prod_smiles)
if prod_lookup is not None:
# skip duplicate products
if prod_smiles not in used:
# Generate a depiction aligned to the reactant template
rdDepictor.GenerateDepictionMatching2DStructure(mol, reactant_template)
output_list.append([mol, name, val])
prod_name, prod_val = prod_lookup
prod_mol.UpdatePropertyCache()
# Generate a depiction aligned to the product template
rdDepictor.GenerateDepictionMatching2DStructure(prod_mol, product_template)
output_list.append([prod_mol, prod_name, prod_val])
used.add(prod_smiles)
return output_list
def testConstrainedCoords(self):
templ = Chem.MolFromSmiles('c1nccc2n1ccc2')
rdDepictor.Compute2DCoords(templ)
m1 = Chem.MolFromSmiles('c1cccc2ncn3cccc3c21')
rdDepictor.GenerateDepictionMatching2DStructure(m1, templ)
m2 = Chem.MolFromSmiles('c1cc(Cl)cc2ncn3cccc3c21')
rdDepictor.Compute2DCoords(m2)
refPatt1 = Chem.MolFromSmarts('*1****2*1***2')
rdDepictor.GenerateDepictionMatching2DStructure(m2, templ, -1, refPatt1)
fileN = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'Depictor', 'test_data',
'1XP0_ligand.sdf')
xp0_lig = Chem.MolFromMolFile(fileN)
xp0_lig_2d = Chem.Mol(xp0_lig)
rdDepictor.GenerateDepictionMatching3DStructure(xp0_lig_2d, xp0_lig)
xp0_ref = Chem.MolFromSmarts('[#6]1~[#7][#6]~[#6]2[#6](=[#8])[#7]~[#6](c3ccccc3)[#7][#7]12')
rdDepictor.GenerateDepictionMatching3DStructure(xp0_lig_2d, xp0_lig, -1, xp0_ref)
def _reorient_molecule(self):
"""Reorients the drawing molecule following the core."""
rdDepictor.GenerateDepictionMatching2DStructure(
self.draw_mol, self.core)
def testGenerate2DDepictionAllowRGroups(self):
templateMolblock = """
RDKit 2D
9 9 0 0 0 0 0 0 0 0999 V2000
-0.8929 1.0942 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.1919 0.3442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.1919 -1.1558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8929 -1.9059 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4060 -1.1558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4060 0.3442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.4910 1.0942 0.0000 R1 0 0 0 0 0 0 0 0 0 0 0 0
1.7051 1.0942 0.0000 R2 0 0 0 0 0 0 0 0 0 0 0 0
-3.4910 -1.9059 0.0000 R3 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
6 8 1 0
3 9 1 0
2 7 1 0
M RGP 3 7 1 8 2 9 3
M END"""
templateRef = Chem.MolFromMolBlock(templateMolblock)
orthoMeta = Chem.MolFromSmiles(
"c1ccc(-c2ccc(-c3ccccc3)c(-c3ccccc3)c2)cc1")
ortho = Chem.MolFromSmiles("c1ccc(-c2ccccc2-c2ccccc2)cc1")
meta = Chem.MolFromSmiles("c1ccc(-c2cccc(-c3ccccc3)c2)cc1")
biphenyl = Chem.MolFromSmiles("c1ccccc1-c1ccccc1")
phenyl = Chem.MolFromSmiles("c1ccccc1")
atomMap = rdDepictor.GenerateDepictionMatching2DStructure(
orthoMeta, templateRef)
self.assertEqual(orthoMeta.GetNumConformers(), 1)
for mol in (ortho, meta, biphenyl, phenyl):
# fails as does not match template
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
mol, templateRef)
# succeeds with allowRGroups=true
atomMap = rdDepictor.GenerateDepictionMatching2DStructure(
mol, templateRef, allowRGroups=True)
self.assertEqual(mol.GetNumConformers(), 1)
msd = 0.0
for refIdx, molIdx in atomMap:
msd += (templateRef.GetConformer().GetAtomPosition(refIdx) -
mol.GetConformer().GetAtomPosition(molIdx)).LengthSq()
msd /= len(atomMap)
self.assertAlmostEqual(msd, 0.0)
# test that using a refPattern with R groups and a reference without works
pyridineRef = Chem.MolFromMolBlock("""
RDKit 2D
6 6 0 0 0 0 0 0 0 0999 V2000
-0.8929 1.0942 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.1919 0.3442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.1919 -1.1558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.8929 -1.9059 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4060 -1.1558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.4060 0.3442 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
M END""")
genericRefPatternWithRGroups = Chem.MolFromSmarts(
"[*:3]a1a([*:1])aa([*:2])aa1")
pyridineRefHs = Chem.AddHs(pyridineRef)
for mol in (ortho, meta, biphenyl, phenyl):
atomMap = rdDepictor.GenerateDepictionMatching2DStructure(
mol,
pyridineRef,
refPatt=genericRefPatternWithRGroups,
allowRGroups=True)
self.assertEqual(mol.GetNumConformers(), 1)
msd = 0.0
for refIdx, molIdx in atomMap:
msd += (pyridineRef.GetConformer().GetAtomPosition(refIdx) -
mol.GetConformer().GetAtomPosition(molIdx)).LengthSq()
msd /= len(atomMap)
self.assertAlmostEqual(msd, 0.0)
def testGenerate2DDepictionRefPatternAtomMap(self):
indazoleMolblock = """
RDKit 2D
9 10 0 0 0 0 0 0 0 0999 V2000
-6.0878 2.4335 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.3867 1.6835 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-7.3867 0.1833 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-6.0878 -0.5666 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.7887 0.1833 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.7887 1.6835 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.4897 -0.5664 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.1906 1.6833 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.1906 0.1835 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1 2 2 0
2 3 1 0
3 4 2 0
4 5 1 0
5 6 2 0
6 1 1 0
8 9 2 0
6 8 1 0
7 9 1 0
7 5 1 0
M END"""
indazoleRef = Chem.MolFromMolBlock(indazoleMolblock)
cycloheptylPyrazole = Chem.MolFromSmiles("c1cc(C2CCCCCC2)[nH]n1")
# test using refPattern
refPatt = Chem.MolFromSmarts("a1aan[nH]1")
rdDepictor.GenerateDepictionMatching2DStructure(cycloheptylPyrazole,
indazoleRef,
refPatt=refPatt)
self.assertEqual(cycloheptylPyrazole.GetNumConformers(), 1)
molMatchVect = cycloheptylPyrazole.GetSubstructMatch(refPatt)
self.assertEqual(len(molMatchVect), refPatt.GetNumAtoms())
refMatchVect = indazoleRef.GetSubstructMatch(refPatt)
self.assertEqual(len(refMatchVect), refPatt.GetNumAtoms())
atomMap = tuple(zip(refMatchVect, molMatchVect))
msd = 0.0
for refIdx, molIdx in atomMap:
msd += (indazoleRef.GetConformer().GetAtomPosition(refIdx) -
cycloheptylPyrazole.GetConformer().GetAtomPosition(molIdx)
).LengthSq()
msd /= len(molMatchVect)
self.assertAlmostEqual(msd, 0.0)
# try with a pattern larger than the reference molecule
hugePatt = Chem.MolFromSmarts("CCCCCCCCCCCCCCCCCCCCCCCCCCC")
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
cycloheptylPyrazole, indazoleRef, refPatt=hugePatt)
# try with an out of range confId
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
cycloheptylPyrazole, indazoleRef, confId=1, refPatt=refPatt)
# test using atomMap directly
cycloheptylPyrazole.RemoveAllConformers()
rdDepictor.GenerateDepictionMatching2DStructure(cycloheptylPyrazole,
indazoleRef,
atomMap=atomMap)
self.assertEqual(cycloheptylPyrazole.GetNumConformers(), 1)
msd = 0.0
for refIdx, molIdx in atomMap:
msd += (indazoleRef.GetConformer().GetAtomPosition(refIdx) -
cycloheptylPyrazole.GetConformer().GetAtomPosition(molIdx)
).LengthSq()
msd /= len(atomMap)
self.assertAlmostEqual(msd, 0.0)
# try with an atomMap larger than the reference molecule
atomMapHuge = list(atomMap) + [
(0, 0) for i in range(indazoleRef.GetNumAtoms())
]
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
cycloheptylPyrazole, indazoleRef, atomMap=atomMapHuge)
# try with an atomMap with out of range indices
atomMapOutOfRange = list(atomMap) + [(100, 100)]
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
cycloheptylPyrazole, indazoleRef, atomMap=atomMapOutOfRange)
# try with an out of range confId
with self.assertRaises(ValueError):
rdDepictor.GenerateDepictionMatching2DStructure(
cycloheptylPyrazole, indazoleRef, atomMap=atomMap, confId=1)