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# Copyright (c) 2023 David Cosgrove and other RDKit contributors
# All rights reserved.
#
# Redistribution and use in source and binary forms, with or without
# modification, are permitted provided that the following conditions are
# met:
#
# * Redistributions of source code must retain the above copyright
# notice, this list of conditions and the following disclaimer.
# * Redistributions in binary form must reproduce the above
# copyright notice, this list of conditions and the following
# disclaimer in the documentation and/or other materials provided
# with the distribution.
# * Neither the name of Novartis Institutes for BioMedical Research Inc.
# nor the names of its contributors may be used to endorse or promote
# products derived from this software without specific prior written
# permission.
#
# THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS
# "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT
# LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR
# A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT
# OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,
# SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT
# LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,
# DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY
# THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
# (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
# OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
#
# These tests are just to check that the Python wrappers are working
# ok. The bulk of the tests are in the C++ code.
import os
import unittest
from pathlib import Path
from rdkit import Chem
from rdkit.Chem import rdRascalMCES
class TestCase(unittest.TestCase):
def setUp(self):
pass
def test1(self):
mol1 = Chem.MolFromSmiles("c1ccccc1Cl")
mol2 = Chem.MolFromSmiles("c1ccccc1F")
opts = rdRascalMCES.RascalOptions()
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(len(results), 1)
self.assertEqual(results[0].smartsString, 'c1:c:c:c:c:c:1')
self.assertEqual(len(results[0].bondMatches()), 6)
self.assertEqual(len(results[0].atomMatches()), 6)
def test2(self):
# Test single largest fragment extraction from results
ad1 = Chem.MolFromSmiles("CN(C)c1ccc(CC(=O)NCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL153934")
ad2 = Chem.MolFromSmiles("N(C)c1ccc(CC(=O)NCCCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL157336")
opts = rdRascalMCES.RascalOptions()
results = rdRascalMCES.FindMCES(ad1, ad2, opts)
self.assertEqual(len(results), 1)
self.assertEqual(results[0].smartsString,
'N(-C)-c1:c:c:c(-CC(=O)-NCCCCCCCCCC):c:c:1.NC12CC3CC(-C1)-CC(-C2)-C3')
results[0].largestFragmentOnly()
self.assertEqual(results[0].smartsString, 'N(-C)-c1:c:c:c(-CC(=O)-NCCCCCCCCCC):c:c:1')
def test3(self):
# Test not specifying options
mol1 = Chem.MolFromSmiles("c1ccccc1Cl")
mol2 = Chem.MolFromSmiles("c1ccccc1F")
results = rdRascalMCES.FindMCES(mol1, mol2)
self.assertEqual(len(results), 1)
self.assertEqual(results[0].smartsString, 'c1:c:c:c:c:c:1')
self.assertEqual(len(results[0].bondMatches()), 6)
self.assertEqual(len(results[0].atomMatches()), 6)
def test4(self):
# Test setting non-default option
mol1 = Chem.MolFromSmiles('Oc1cccc2C(=O)C=CC(=O)c12')
mol2 = Chem.MolFromSmiles('O1C(=O)C=Cc2cc(OC)c(O)cc12')
results = rdRascalMCES.FindMCES(mol1, mol2)
self.assertEqual(len(results), 0)
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.5
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(len(results), 1)
def test5(self):
# Test setting non-default option singleLargestFrag
ad1 = Chem.MolFromSmiles("CN(C)c1ccc(CC(=O)NCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL153934")
ad2 = Chem.MolFromSmiles("N(C)c1ccc(CC(=O)NCCCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL157336")
opts = rdRascalMCES.RascalOptions()
opts.singleLargestFrag = True
results = rdRascalMCES.FindMCES(ad1, ad2, opts)
self.assertEqual(len(results), 1)
self.assertEqual(results[0].smartsString, 'CCCCCCCCCCNC12CC3CC(-C1)-CC(-C2)-C3')
def test6(self):
# Test the threshold and examine the tier1 and tier2 similarities.
ad1 = Chem.MolFromSmiles("CN(C)c1ccc(CC(=O)NCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL153934")
ad2 = Chem.MolFromSmiles("N(C)c1ccc(CC(=O)NCCCCCCCCCCCCNC23CC4CC(C2)CC(C3)C4)cc1 CHEMBL157336")
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.95
results = rdRascalMCES.FindMCES(ad1, ad2, opts)
self.assertEqual(len(results), 0)
opts.returnEmptyMCES = True
results = rdRascalMCES.FindMCES(ad1, ad2, opts)
self.assertEqual(len(results), 1)
def testRascalCluster(self):
cdk2_file = Path(os.environ['RDBASE']) / 'Contrib' / 'Fastcluster' / 'cdk2.smi'
suppl = Chem.SmilesMolSupplier(str(cdk2_file), '\t', 1, 0, False)
mols = [mol for mol in suppl]
clusters = rdRascalMCES.RascalCluster(mols)
self.assertEqual(len(clusters), 8)
expClusters = [7, 7, 6, 2, 2, 2, 2, 20]
for clus, expClusSize in zip(clusters, expClusters):
self.assertEqual(expClusSize, len(clus))
clusOpts = rdRascalMCES.RascalClusterOptions()
clusOpts.similarityCutoff = 0.6
clusters = rdRascalMCES.RascalCluster(mols, clusOpts)
expClusters = [9, 8, 6, 2, 2, 2, 2, 2, 2, 2, 11]
for clus, expClusSize in zip(clusters, expClusters):
self.assertEqual(expClusSize, len(clus))
def testRascalButinaCluster(self):
cdk2_file = Path(os.environ['RDBASE']) / 'Contrib' / 'Fastcluster' / 'cdk2.smi'
suppl = Chem.SmilesMolSupplier(str(cdk2_file), '\t', 1, 0, False)
mols = [mol for mol in suppl]
clusters = rdRascalMCES.RascalButinaCluster(mols)
self.assertEqual(len(clusters), 29)
expClusters = [
6, 6, 6, 2, 2, 2, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1
]
for clus, expClusSize in zip(clusters, expClusters):
self.assertEqual(expClusSize, len(clus))
def testMaxBondMatchPairs(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.0
opts.returnEmptyMCES = True
opts.singleLargestFrag = True
opts.allBestMCESs = True
opts.completeAromaticRings = False
opts.timeout = -1
too_long_1 = Chem.MolFromSmiles('CCCC=CCCCC=CCCCCCCCCCCCCCCCCCCCCC1CNCCC1')
too_long_2 = Chem.MolFromSmiles('CCCC=CCCCCC=CCCCCCCCCCCCCCCCCCCCC1CNCCC1')
results = rdRascalMCES.FindMCES(too_long_1, too_long_2, opts)
self.assertEqual(len(results[0].bondMatches()), 0)
opts.maxBondMatchPairs = 1200
results = rdRascalMCES.FindMCES(too_long_1, too_long_2, opts)
self.assertEqual(len(results[0].bondMatches()), 26)
def testExactConnectionsMatch(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.5
opts.allBestMCESs = True
mol1 = Chem.MolFromSmiles('c1ccccc1C1CCC(C(C)C)C1')
mol2 = Chem.MolFromSmiles('c1ccccc1C(C)C')
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(results[0].numFragments, 1)
self.assertEqual(results[0].smartsString, 'c1:c:c:c:c:c:1-C(-C)-C')
opts.exactConnectionsMatch = True
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(results[0].numFragments, 2)
self.assertEqual(results[0].smartsString,
'[#6&a&D2]1:[#6&a&D2]:[#6&a&D2]:[#6&a&D2]:[#6&a&D2]:[#6&a&D3]:1.[#6&A&D3](-[#6&A&D1])-[#6&A&D1]')
def testEquivalentAtoms(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.5
opts.equivalentAtoms = "[F,Cl,Br,I]"
mol1 = Chem.MolFromSmiles('c1ccccc1F')
mol2 = Chem.MolFromSmiles('c1ccccc1Br')
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(results[0].numFragments, 1)
self.assertEqual(results[0].smartsString, 'c1:c:c:c:c:c:1-[F,Cl,Br,I]')
def testEquivalentBonds(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.5
opts.ignoreBondOrders = True
mol1 = Chem.MolFromSmiles('CC=CC')
mol2 = Chem.MolFromSmiles('CCCC')
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(results[0].numFragments, 1)
self.assertEqual(results[0].smartsString, 'C~C~C~C')
def testExactAtomTypeMatch(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.1
opts.ignoreAtomAromaticity = False
mol1 = Chem.MolFromSmiles('c1ccccc1NCC')
mol2 = Chem.MolFromSmiles('C1CCCCC1NCC')
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertEqual(results[0].numFragments, 1)
self.assertEqual(results[0].smartsString, 'NCC')
def testMinCliqueSize(self):
opts = rdRascalMCES.RascalOptions()
opts.similarityThreshold = 0.1
opts.minCliqueSize = 17
mol1 = Chem.MolFromSmiles('CC12CCC3C(C1CCC2O)CCC4=CC(=O)CCC34C')
mol2 = Chem.MolFromSmiles('CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)O')
results = rdRascalMCES.FindMCES(mol1, mol2, opts)
self.assertFalse(results)
if __name__ == "__main__":
unittest.main()
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