# Copyright (c) 2018-2021, Novartis Institutes for BioMedical Research Inc. # 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. # import unittest from collections import OrderedDict import json import itertools # the RGD code can generate a lot of warnings. disable them from rdkit import Chem, RDLogger, rdBase from rdkit.Chem.rdRGroupDecomposition import (RGroupCoreAlignment, RGroupDecompose, RGroupDecomposition, RGroupDecompositionParameters, RGroupLabels, RGroupLabelling, RelabelMappedDummies) RDLogger.DisableLog("rdApp.warning") class TestCase(unittest.TestCase): def test_multicores(self): cores_smi_easy = OrderedDict() cores_smi_hard = OrderedDict() # cores_smi_easy['cephem'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)=C([3*])CS2') cores_smi_easy['cephem'] = Chem.MolFromSmarts('O=C1C([*:1])C2N1C(C(O)=O)=C([*:3])CS2') cores_smi_hard['cephem'] = Chem.MolFromSmarts('O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)=C([3*])CS2') # cores_smi_easy['carbacephem'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)=C([3*])CC2') cores_smi_easy['carbacephem'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)=C([3*])CC2') cores_smi_hard['carbacephem'] = Chem.MolFromSmarts( 'O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)=C([3*])CC2') # cores_smi_easy['oxacephem'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)=C([3*])CO2') cores_smi_easy['oxacephem'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)=C([3*])CO2') cores_smi_hard['oxacephem'] = Chem.MolFromSmarts( 'O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)=C([3*])CO2') # cores_smi_easy['carbapenem'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)=C([3*])C2') cores_smi_easy['carbapenem'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)=C([3*])C2') cores_smi_hard['carbapenem'] = Chem.MolFromSmarts( 'O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)=C([3*])C2') # cores_smi_easy['carbapenam'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)C([3*])([4*])C2') cores_smi_easy['carbapenam'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)C([3*])([4*])C2') cores_smi_hard['carbapenam'] = Chem.MolFromSmarts( 'O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)C([3*])([4*])C2') # cores_smi_easy['penem'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)=C([3*])S2') cores_smi_easy['penem'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)=C([3*])S2') cores_smi_hard['penem'] = Chem.MolFromSmarts('O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)=C([3*])S2') # cores_smi_easy['penam'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)C([3*])([4*])S2') cores_smi_easy['penam'] = Chem.MolFromSmarts('O=C1C([*:1])C2N1C(C(O)=O)C([*:3])([*:4])S2') cores_smi_hard['penam'] = Chem.MolFromSmarts( 'O=C1C([*:2])([*:1])[C@@H]2N1C(C(O)=O)C([*:3])([*:4])S2') # cores_smi_easy['oxapenam'] = Chem.MolFromSmiles('O=C1C([1*])[C@@H]2N1C(C(O)=O)C([3*])([4*])O2') cores_smi_easy['oxapenam'] = Chem.MolFromSmarts('O=C1C([1*])C2N1C(C(O)=O)C([3*])([4*])O2') cores_smi_hard['oxapenam'] = Chem.MolFromSmarts( 'O=C1C([2*])([1*])[C@@H]2N1C(C(O)=O)C([3*])([4*])O2') cores_smi_easy['monobactam'] = Chem.MolFromSmarts('O=C1C([1*])C([5*])N1') cores_smi_hard['monobactam'] = Chem.MolFromSmarts('O=C1C([2*])([1*])C([6*])([5*])N1') rg_easy = RGroupDecomposition(cores_smi_easy.values()) rg_stereo = RGroupDecomposition(cores_smi_hard.values()) def test_stereo(self): smiles = """C1CCO[C@@H](N)1 C1CCO[C@H](N)1 C1CCO[C@@](N)(O)1 C1CCO[C@@](N)(P)1 C1CCO[C@@](N)(S)1 C1CCO[C@@H](O)1 C1CCO[C@H](O)1 C1CCO[C@@](O)(N)1 C1CCO[C@@](O)(P)1 C1CCO[C@@](O)(S)1 C1CCO[C@@H](P)1 C1CCO[C@H](P)1 C1CCO[C@@](P)(N)1 C1CCO[C@@](P)(O)1 C1CCO[C@@](P)(S)1 C1CCO[C@@H](S)1 C1CCO[C@H](S)1 C1CCO[C@@](S)(N)1 C1CCO[C@@](S)(O)1 C1CCO[C@@](S)(P)1 """ mols = [] for smi in smiles.split(): m = Chem.MolFromSmiles(smi) assert m, smi mols.append(m) core = Chem.MolFromSmarts("C1CCOC1") rgroups = RGroupDecomposition(core) for m in mols: rgroups.Add(m) rgroups.Process() columns = rgroups.GetRGroupsAsColumns() data = {} for k, v in columns.items(): data[k] = [Chem.MolToSmiles(m, True) for m in v] rgroups2, unmatched = RGroupDecompose([core], mols) columns2, unmatched = RGroupDecompose([core], mols, asRows=False) data2 = {} for k, v in columns2.items(): data2[k] = [Chem.MolToSmiles(m, True) for m in v] self.assertEqual(data, data2) columns3, unmatched = RGroupDecompose([core], mols, asRows=False, asSmiles=True) self.assertEqual(data, columns3) def test_h_options(self): core = Chem.MolFromSmiles("O=c1oc2ccccc2cc1") smiles = ("O=c1cc(Cn2ccnc2)c2ccc(Oc3ccccc3)cc2o1", "O=c1oc2ccccc2c(Cn2ccnc2)c1-c1ccccc1", "COc1ccc2c(Cn3cncn3)cc(=O)oc2c1") params = RGroupDecompositionParameters() rgd = RGroupDecomposition(core, params) for smi in smiles: m = Chem.MolFromSmiles(smi) rgd.Add(m) rgd.Process() columns = rgd.GetRGroupsAsColumns() self.assertEqual(columns['R2'][0].GetNumAtoms(), 7) params.removeHydrogensPostMatch = False rgd = RGroupDecomposition(core, params) for smi in smiles: m = Chem.MolFromSmiles(smi) rgd.Add(m) rgd.Process() columns = rgd.GetRGroupsAsColumns() self.assertEqual(columns['R2'][0].GetNumAtoms(), 12) def test_unmatched(self): cores = [Chem.MolFromSmiles("N")] mols = [ Chem.MolFromSmiles("CC"), Chem.MolFromSmiles("CC"), Chem.MolFromSmiles("CC"), Chem.MolFromSmiles("N"), Chem.MolFromSmiles("CC") ] res, unmatched = RGroupDecompose(cores, mols) self.assertEqual(len(res), 1) self.assertEqual(unmatched, [0, 1, 2, 4]) def test_userlabels(self): smis = ["C(Cl)N(N)O(O)"] mols = [Chem.MolFromSmiles(smi) for smi in smis] smarts = 'C([*:1])N([*:5])O([*:6])' core = Chem.MolFromSmarts(smarts) rg = RGroupDecomposition(core) for m in mols: rg.Add(m) rg.Process() self.assertEqual(rg.GetRGroupsAsColumns(asSmiles=True), { 'Core': ['C(N(O[*:6])[*:5])[*:1]'], 'R1': ['Cl[*:1]'], 'R5': ['N[*:5]'], 'R6': ['O[*:6]'] }) smarts = 'C([*:4])N([*:5])O([*:6])' core = Chem.MolFromSmarts(smarts) rg = RGroupDecomposition(core) for m in mols: rg.Add(m) rg.Process() self.assertEqual(rg.GetRGroupsAsColumns(asSmiles=True), { 'Core': ['C(N(O[*:6])[*:5])[*:4]'], 'R4': ['Cl[*:4]'], 'R5': ['N[*:5]'], 'R6': ['O[*:6]'] }) def test_match_only_at_rgroups(self): smiles = ['c1ccccc1'] # , 'c1(Cl)ccccc1', 'c1(Cl)cc(Br)ccc1'] mols = [Chem.MolFromSmiles(smi) for smi in smiles] core1 = Chem.MolFromSmiles("c1([*:5])cc([*:6])ccc1") params = RGroupDecompositionParameters() params.onlyMatchAtRGroups = True rg = RGroupDecomposition(core1, params) for smi, m in zip(smiles, mols): self.assertTrue(rg.Add(m) != -1, smi) def test_incorrect_multiple_rlabels(self): mols = [Chem.MolFromSmiles(smi) for smi in ( "C1NC(Cl)CC1", "C1OC(Cl)CC1", "C1(Cl)OCCC1", )] scaffolds = [Chem.MolFromSmarts(x) for x in ("C1NCCC1", )] groups, unmatched = RGroupDecompose(scaffolds, mols, asSmiles=True, asRows=False) self.assertEqual(groups, {'Core': ['C1CNC([*:1])C1'], 'R1': ['Cl[*:1]']}) scaffolds = [Chem.MolFromSmarts(x) for x in ("C1OCCC1", )] groups, unmatched = RGroupDecompose(scaffolds, mols, asSmiles=True, asRows=False) self.assertEqual(groups, { 'Core': ['C1COC([*:1])C1', 'C1COC([*:1])C1'], 'R1': ['Cl[*:1]', 'Cl[*:1]'] }) scaffolds = [Chem.MolFromSmarts(x) for x in ("C1NCCC1", "C1OCCC1")] groups, unmatched = RGroupDecompose(scaffolds, mols, asSmiles=True, asRows=False) self.assertEqual( groups, { 'Core': ['C1CNC([*:1])C1', 'C1COC([*:1])C1', 'C1COC([*:1])C1'], 'R1': ['Cl[*:1]', 'Cl[*:1]', 'Cl[*:1]'] }) def test_aligned_cores(self): scaffolds = [Chem.MolFromSmarts(x) for x in ("C1NC1OC", "C1NC1NC")] mols = [Chem.MolFromSmiles(smi) for smi in ("C1NC1OCCC", "C1NC1NCCC")] groups, unmatched = RGroupDecompose(scaffolds, mols, asSmiles=True, asRows=True) # print("test_aligned_Cores") # print("groups:", groups) self.assertEqual(groups, [{ 'Core': 'C1NC1OC[*:1]', 'R1': 'CC[*:1]' }, { 'Core': 'C1NC1NC[*:2]', 'R2': 'CC[*:2]' }]) def test_aligned_cores2(self): scaffolds = [Chem.MolFromSmarts(x) for x in ("C1NCC1", "C1SCC1")] mols = [Chem.MolFromSmiles(smi) for smi in ("C1N(P)CC1", "C1S(P)CC1")] # print("test_aligned_Cores2") groups, unmatched = RGroupDecompose(scaffolds, mols, asSmiles=True, asRows=True) # print("groups: ", groups) self.assertEqual(groups, [{ 'Core': 'C1CN([*:1])C1', 'R1': 'P[*:1]' }, { 'Core': 'C1C[SH]([*:2])C1', 'R2': 'P[*:2]' }]) def test_getrgrouplabels(self): smis = ["C(Cl)N(N)O(O)"] mols = [Chem.MolFromSmiles(smi) for smi in smis] smarts = 'C([*:1])N([*:5])O([*:6])' core = Chem.MolFromSmarts(smarts) rg = RGroupDecomposition(core) for m in mols: rg.Add(m) rg.Process() self.assertEqual(set(rg.GetRGroupLabels()), set(rg.GetRGroupsAsColumns())) def test_timeout(self): smis = '''CN(C)Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 CNc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 Cc1cc2cc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)ccc2[nH]1 Cc1cc2cc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc2[nH]1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccccc1Cl O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(Cl)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc([N+](=O)[O-])c1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(CO)c1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccccc2Cl)cc1[N+](=O)[O-] O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(Cl)cc1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(Cl)c2)cc1[N+](=O)[O-] CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccc(Cl)cc2)cc1[N+](=O)[O-] CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc3c2ccn3C)cc1[N+](=O)[O-] CC(=O)Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 COc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 CN(C)c1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 N#Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 Cc1nc2ccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)cc2s1 Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc2s1 Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN(C)C)c([N+](=O)[O-])c3)ccc2s1 CN(C)C(=O)CCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)C(=O)Cc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)CCCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)CCc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)C(=O)c1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)Cc1ccccc1Oc1cc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)ccc1C(=O)NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(N3CCOCC3)c2)cc1[N+](=O)[O-] Cc1nc(C)c(-c2cccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c2)s1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(Cl)cc(Cl)c3)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Cl)c3)cc2[N+](=O)[O-])CC1 CN(C)CCOc1ccc(-c2ccc(Cl)cc2)c(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C)CC5)c([N+](=O)[O-])c4)c(Oc4cccc(Cl)c4)c3)CC2)c1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)OC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 CN(C)CCOc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccc(N)c(Cl)c3)cc2[N+](=O)[O-])CC1 CC(C)N1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Br)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCCC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 Cc1n[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c12 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(F)c3F)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Br)c3)cc2[N+](=O)[O-])CC1 CCN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 CN1C(C)(C)CC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1(C)C CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C6CCOCC6)CC5)c([N+](=O)[O-])c4)c(Oc4cccc(F)c4F)c3)CC2)=C(c2ccc(Cl)cc2)C1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(F)c4[nH]ccc4c3)cc2[N+](=O)[O-])CC1 CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cccc(F)c4F)c3)CC2)=C(c2ccc(Cl)cc2)C1 CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4ccc(N)c(Cl)c4)c3)CC2)=C(c2ccc(Cl)cc2)C1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3cc(CCN4CCCC4)ccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(Cl)c1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(Cl)c3Cl)cc2[N+](=O)[O-])CC1 Cc1n[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)c12 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCCCC5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(C(F)(F)F)c3)cc2[N+](=O)[O-])CC1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc3c2CCC(=O)N3)cc1[N+](=O)[O-] CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccccc3Cl)cc2S(=O)(=O)C(F)(F)F)CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cc(Cl)ccc3Cl)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3ccc(F)cc3Cl)cc2[N+](=O)[O-])CC1 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)C5)CC4)cc3Oc3ccccc3Cl)cc2[N+](=O)[O-])CC1 Cc1c[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)c12 CN1CCC(Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)cc3Oc3cccc(C(F)(F)F)c3Cl)cc2[N+](=O)[O-])CC1 CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC5CCN(C6CC6)CC5)c([N+](=O)[O-])c4)c(Oc4ccccc4Cl)c3)CC2)=C(c2ccc(Cl)cc2)C1 Cc1c[nH]c2cccc(Oc3cc(N4CCN(CC5=C(c6ccc(Cl)cc6)CC(C)(C)CC5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NC4CCN(C)CC4)c([N+](=O)[O-])c3)c12 CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCN5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cc(Cl)ccc4Cl)c3)CC2)=C(c2ccc(Cl)cc2)C1 Cn1ccc2c(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)cccc21 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(N2CCOCC2)c1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2ccc3[nH]cc(CCC(=O)N4CCOCC4)c3c2)cc1[N+](=O)[O-] O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(OCc2ccccc2)c1 N#Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc2[nH]cc(CCC(=O)N3CCOCC3)c2c1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc2[nH]cc(CCCN3CCOCC3)c2c1 CN(C)Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-n2ccnc2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)cc1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc([N+](=O)[O-])c1 CCN(Cc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1)C(=O)OC(C)(C)C CCN(Cc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1)C(=O)OC(C)(C)C CCNCc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 CCNCc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 CC(=O)Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 CC(C)(C)OC(=O)Nc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccccc1-c1ccccc1 CC(C)(C)OC(=O)Nc1cccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)c1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(-c2ccccc2)c1 CN(C)CCc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCc2ccccc2)cc1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(N2CCOCC2)c1 Cc1nc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)ccc2s1 CC(C)(C)OC(=O)N1CCN(c2cccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCC4CCOCC4)c([N+](=O)[O-])c3)c2)CC1 CN(C)CCCNc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)cc2Oc2cccc(OCc3ccccc3)c2)cc1[N+](=O)[O-] O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(OCc2ccccc2)c1 O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCCN2CCOCC2)cc1 O=C1CCc2c(cccc2Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)N1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(OCc2ccccc2)cc1 CC(C)(C)OC(=O)N1CCN(c2ccc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)cc2)CC1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1cccc(-c2ccncc2)c1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-c2ccncc2)cc1 O=C(NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccc(-c2cccnc2)cc1 CN(C)C(=O)COc1ccc(Oc2cc(N3CCN(Cc4ccccc4-c4ccc(Cl)cc4)CC3)ccc2C(=O)NS(=O)(=O)c2ccc(NCC3CCOCC3)c([N+](=O)[O-])c2)cc1 Cn1cnc2cc(Oc3cc(N4CCN(Cc5ccccc5-c5ccc(Cl)cc5)CC4)ccc3C(=O)NS(=O)(=O)c3ccc(NCCCN4CCOCC4)c([N+](=O)[O-])c3)ccc21''' mols = [Chem.MolFromSmiles(x) for x in smis.split('\n')] core = Chem.MolFromSmarts('O=C(NS(=O)(=O)c1ccccc1)c1ccccc1Oc1ccccc1') ps = RGroupDecompositionParameters() ps.timeout = 0.1 res = None with self.assertRaises(RuntimeError): rg = RGroupDecomposition(core, ps) for m in mols: res = rg.Add(m) self.assertIsNotNone(res) self.assertGreater(res, 0) with self.assertRaises(RuntimeError): columns2, unmatched = RGroupDecompose([core], mols, asRows=False, options=ps) def test_github3402(self): core1 = "[$(C-!@[a])](=O)(Cl)" sma = Chem.MolFromSmarts(core1) m = Chem.MolFromSmiles("c1ccccc1C(=O)Cl") self.assertEqual(RGroupDecompose(sma, [m], asSmiles=True), ([{ 'Core': 'O=C(Cl)[*:1]', 'R1': 'c1ccc([*:1])cc1' }], [])) def test_multicore_prelabelled(self): def multicorergd_test(cores, params, expected_rows, expected_items): mols = [Chem.MolFromSmiles(smi) for smi in ("CNC(=O)C1=CN=CN1CC", "Fc1ccc2ccc(Br)nc2n1")] params.removeHydrogensPostMatch = True params.onlyMatchAtRGroups = True decomp = RGroupDecomposition(cores, params) i = 0 for i, m in enumerate(mols): res = decomp.Add(m) self.assertEqual(res, i) self.assertTrue(decomp.Process()) rows = decomp.GetRGroupsAsRows(asSmiles=True) self.assertEqual(rows, expected_rows) items = decomp.GetRGroupsAsColumns(asSmiles=True) self.assertEqual(items, expected_items) sdcores = """ RDKit 2D 9 9 0 0 0 0 0 0 0 0999 V2000 1.1100 -1.3431 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5225 -0.6286 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9705 -0.0156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2168 -0.3511 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3029 -1.1716 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1419 0.7914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5289 1.3431 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9266 1.0463 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 -0.4976 0.0613 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 1 5 2 0 3 6 1 0 6 7 2 0 6 8 1 0 4 9 1 0 M RGP 2 8 1 9 2 V 8 * V 9 * M END $$$$ RDKit 2D 12 13 0 0 0 0 0 0 0 0999 V2000 -6.5623 0.3977 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 -5.8478 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1333 0.3977 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0 -4.4188 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4188 -0.8397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1333 -1.2522 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0 -5.8478 -0.8397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7044 -1.2522 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0 -3.7044 0.3977 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.9899 -0.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9899 -0.8397 0.0000 A 0 0 0 0 0 0 0 0 0 0 0 0 -2.2754 0.3978 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 2 3 2 0 2 7 1 0 9 10 2 0 10 11 1 0 8 11 2 0 8 5 1 0 4 9 1 0 10 12 1 0 1 2 1 0 M RGP 2 1 2 12 1 V 1 * V 12 * M END $$$$ """ sdsup = Chem.SDMolSupplier() sdsup.SetData(sdcores) cores = [c for c in sdsup] expected_rows = [{ 'Core': 'O=C(c1cncn1[*:2])[*:1]', 'R1': 'CN[*:1]', 'R2': 'CC[*:2]' }, { 'Core': 'c1cc2ccc([*:2])nc2nc1[*:1]', 'R1': 'F[*:1]', 'R2': 'Br[*:2]' }] expected_items = { 'Core': ['O=C(c1cncn1[*:2])[*:1]', 'c1cc2ccc([*:2])nc2nc1[*:1]'], 'R1': ['CN[*:1]', 'F[*:1]'], 'R2': ['CC[*:2]', 'Br[*:2]'] } params = RGroupDecompositionParameters() # test pre-labelled with MDL R-group labels, autodetect params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with MDL R-group labels, no autodetect params.labels = RGroupLabels.MDLRGroupLabels | RGroupLabels.RelabelDuplicateLabels params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with MDL R-group labels, autodetect, no MCS alignment params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.NoAlignment multicorergd_test(cores, params, expected_rows, expected_items) # Reading from a MDL molblock also sets isotopic labels, so no need # to set them again; we only clear MDL R-group labels for core in cores: for a in core.GetAtoms(): if a.HasProp("_MolFileRLabel"): a.ClearProp("_MolFileRLabel") # test pre-labelled with isotopic labels, autodetect params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with isotopic labels, no autodetect params.labels = RGroupLabels.IsotopeLabels | RGroupLabels.RelabelDuplicateLabels params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with isotopic labels, autodetect, no MCS alignment params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.NoAlignment multicorergd_test(cores, params, expected_rows, expected_items) for core in cores: for a in core.GetAtoms(): iso = a.GetIsotope() if iso: a.SetAtomMapNum(iso) a.SetIsotope(0) # test pre-labelled with atom map labels, autodetect params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with atom map labels, no autodetect params.labels = RGroupLabels.AtomMapLabels | RGroupLabels.RelabelDuplicateLabels params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with atom map labels, autodetect, no MCS alignment params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.NoAlignment multicorergd_test(cores, params, expected_rows, expected_items) for core in cores: for a in core.GetAtoms(): if a.GetAtomMapNum(): a.SetAtomMapNum(0) # test pre-labelled with dummy atom labels, autodetect expected_rows = [{ 'Core': 'O=C(c1cncn1[*:2])[*:1]', 'R1': 'CN[*:1]', 'R2': 'CC[*:2]' }, { 'Core': 'c1cc2ccc([*:2])nc2nc1[*:1]', 'R1': 'Br[*:1]', 'R2': 'F[*:2]' }] expected_items = { 'Core': ['O=C(c1cncn1[*:2])[*:1]', 'c1cc2ccc([*:2])nc2nc1[*:1]'], 'R1': ['CN[*:1]', 'Br[*:1]'], 'R2': ['CC[*:2]', 'F[*:2]'] } params.labels = RGroupLabels.AutoDetect params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) # test pre-labelled with dummy atom labels, no autodetect # in this case there is no difference from autodetect as the RGD code # cannot tell the difference between query atoms and dummy R-groups params.labels = RGroupLabels.DummyAtomLabels | RGroupLabels.RelabelDuplicateLabels params.alignment = RGroupCoreAlignment.MCS multicorergd_test(cores, params, expected_rows, expected_items) def testRemoveAllHydrogenFlags(self): core = Chem.MolFromSmiles("[1*]c1ccc([2*])cn1") mol = Chem.MolFromSmiles("Fc1ccccn1") params = RGroupDecompositionParameters() rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.Add(mol), 0) self.assertTrue(rgd.Process()) res = rgd.GetRGroupsAsColumns(asSmiles=True) self.assertEqual(res, {'Core': ['c1ccc([*:1])nc1'], 'R1': ['F[*:1]']}) # no change, as removeAllHydrogenRGroupsAndLabels is True params = RGroupDecompositionParameters() params.removeAllHydrogenRGroups = False rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.Add(mol), 0) self.assertTrue(rgd.Process()) res = rgd.GetRGroupsAsColumns(asSmiles=True) self.assertEqual(res, {'Core': ['c1ccc([*:1])nc1'], 'R1': ['F[*:1]']}) # Unused user-defined labels retained on core # R groups still retained as removeAllHydrogenRGroups is True params = RGroupDecompositionParameters() params.removeAllHydrogenRGroupsAndLabels = False rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.Add(mol), 0) self.assertTrue(rgd.Process()) res = rgd.GetRGroupsAsColumns(asSmiles=True) self.assertEqual(res, {'Core': ['c1cc([*:1])ncc1[*:2]'], 'R1': ['F[*:1]']}) # Unused user-defined labels retained on core and in R groups params = RGroupDecompositionParameters() params.removeAllHydrogenRGroups = False params.removeAllHydrogenRGroupsAndLabels = False rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.Add(mol), 0) self.assertTrue(rgd.Process()) res = rgd.GetRGroupsAsColumns(asSmiles=True) self.assertEqual(res, {'Core': ['c1cc([*:1])ncc1[*:2]'], 'R1': ['F[*:1]'], 'R2': ['[H][*:2]']}) def testSubstructMatchParameters(self): mols = [ Chem.MolFromSmiles(x) for x in ("C1CN[C@H]1F", "C1CN[C@]1(O)F", "C1CN[C@@H]1F", "C1CN[CH]1F") ] cores = [Chem.MolFromSmiles('C1CNC1[*:1]')] chiral_cores = [Chem.MolFromSmiles('C1CN[C@H]1[*:1]')] rgroups, unmatched = RGroupDecompose(cores, mols) self.assertEqual(unmatched, []) rgroups, unmatched = RGroupDecompose(chiral_cores, mols) self.assertEqual(unmatched, [3]) params = RGroupDecompositionParameters() params.substructMatchParams.useChirality = False rgroups, unmatched = RGroupDecompose(cores, mols, options=params) self.assertEqual(unmatched, []) rgroups, unmatched = RGroupDecompose(chiral_cores, mols, options=params) self.assertEqual(unmatched, []) def testTautomerCore(self): block = """" Mrv2008 08072313382D 9 9 0 0 0 0 999 V2000 5.9823 5.0875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9823 4.2625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2679 3.8500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5534 4.2625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5534 5.0875 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.2679 5.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2679 6.3250 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6968 3.8500 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 5.2679 3.0250 0.0000 R# 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 1 6 1 0 0 0 0 2 8 1 0 0 0 0 3 9 1 0 0 0 0 M RGP 2 8 1 9 2 M END """ core = Chem.MolFromMolBlock(block) mol1 = Chem.MolFromSmiles('Cc1cnc(O)cc1Cl') mol2 = Chem.MolFromSmiles('CC1=CNC(=O)C=C1F') params = RGroupDecompositionParameters() params.doTautomers = True rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.Add(mol1), 0) self.assertEqual(rgd.Add(mol2), 1) self.assertTrue(rgd.Process()) rows = rgd.GetRGroupsAsRows(asSmiles=True) expected_rows = [ {'Core': 'Oc1cc([*:1])c([*:2])cn1', 'R1': 'Cl[*:1]', 'R2': 'C[*:2]'}, {'Core': 'O=c1cc([*:1])c([*:2])c[nH]1', 'R1': 'F[*:1]', 'R2': 'C[*:2]'}] self.assertEqual(rows, expected_rows) def testMolMatchesCore(self): core = Chem.MolFromSmarts("[*:1]c1[!#1]([*:2])cc([*:3])n([*:4])c(=O)1") cmol = Chem.MolFromSmiles("Clc1c(C)cc(F)n(CC)c(=O)1") nmol = Chem.MolFromSmiles("Clc1ncc(F)n(CC)c(=O)1") smol = Chem.MolFromSmiles("Clc1ncc(F)n(CC)c(=S)1") params = RGroupDecompositionParameters() params.onlyMatchAtRGroups = True rgd = RGroupDecomposition(core, params) self.assertEqual(rgd.GetMatchingCoreIdx(cmol), 0) self.assertEqual(rgd.GetMatchingCoreIdx(nmol), 0) self.assertEqual(rgd.GetMatchingCoreIdx(smol), -1) matches = [] self.assertEqual(rgd.GetMatchingCoreIdx(cmol, matches), 0) self.assertEqual(len(matches), 1) self.assertEqual(len(matches[0]), core.GetNumAtoms()) matches = [] self.assertEqual(rgd.GetMatchingCoreIdx(nmol, matches), 0) self.assertEqual(len(matches), 1) self.assertEqual(len(matches[0]), core.GetNumAtoms() - 1) matches = [] self.assertEqual(rgd.GetMatchingCoreIdx(smol, matches), -1) self.assertEqual(len(matches), 0) cmol_h = Chem.AddHs(cmol) nmol_h = Chem.AddHs(nmol) self.assertTrue(cmol_h.HasSubstructMatch(core)) self.assertEqual(len(cmol_h.GetSubstructMatch(core)), core.GetNumAtoms()) self.assertFalse(nmol_h.HasSubstructMatch(core)) def testRelabelMappedDummies(self): p = Chem.SmilesWriteParams() p.canonical = False allDifferentCore = Chem.MolFromMolBlock(""" RDKit 2D 8 8 0 0 0 0 0 0 0 0999 V2000 1.0808 -0.8772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0827 0.1228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2177 0.6246 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2198 1.6246 0.0000 R# 0 0 0 0 0 15 0 0 0 4 0 0 -0.6493 0.1262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5142 0.6280 0.0000 R# 0 0 0 0 0 15 0 0 0 3 0 0 -0.6513 -0.8736 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2137 -1.3754 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 1 0 3 5 2 0 5 6 1 0 5 7 1 0 7 8 2 0 8 1 1 0 M RGP 2 4 2 6 1 M END )CTAB """) allDifferentCore.RemoveConformer(0) allDifferentCore.GetAtomWithIdx(3).SetIsotope(6) allDifferentCore.GetAtomWithIdx(5).SetIsotope(5) self.assertEqual(Chem.MolToCXSmiles(allDifferentCore, p), "c1cc([6*:4])c([5*:3])cn1 |atomProp:3.dummyLabel.R2:3.molAtomMapNumber.4:5.dummyLabel.R1:5.molAtomMapNumber.3|") # AtomMap in, MDLRGroup out core = Chem.MolFromSmiles("c1cc([*:2])c([*:1])cn1") self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([*:2])c([*:1])cn1 |atomProp:3.dummyLabel.*:3.molAtomMapNumber.2:5.dummyLabel.*:5.molAtomMapNumber.1|") RelabelMappedDummies(core) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") # Isotope in, MDLRGroup out core = Chem.MolFromSmiles("c1cc([2*])c([1*])cn1") self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([2*])c([1*])cn1 |atomProp:3.dummyLabel.*:5.dummyLabel.*|") RelabelMappedDummies(core) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") # MDLRGroup in, MDLRGroup out core = Chem.MolFromMolBlock(""" RDKit 2D 8 8 0 0 0 0 0 0 0 0999 V2000 1.0808 -0.8772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0827 0.1228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2177 0.6246 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2198 1.6246 0.0000 R# 0 0 0 0 0 1 0 0 0 0 0 0 -0.6493 0.1262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5142 0.6280 0.0000 R# 0 0 0 0 0 1 0 0 0 0 0 0 -0.6513 -0.8736 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2137 -1.3754 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 1 0 3 5 2 0 5 6 1 0 5 7 1 0 7 8 2 0 8 1 1 0 M RGP 2 4 2 6 1 M END )CTAB """) core.RemoveConformer(0) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([2*])c([1*])cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") RelabelMappedDummies(core) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") # AtomMap and Isotope in, MDLRGroup out - AtomMap has priority core = Chem.MolFromSmiles("c1cc([4*:2])c([3*:1])cn1") self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([4*:2])c([3*:1])cn1 |atomProp:3.dummyLabel.*:3.molAtomMapNumber.2:5.dummyLabel.*:5.molAtomMapNumber.1|") RelabelMappedDummies(core) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") # AtomMap and Isotope in, MDLRGroup out - force Isotope priority core = Chem.MolFromSmiles("c1cc([4*:2])c([3*:1])cn1") self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([4*:2])c([3*:1])cn1 |atomProp:3.dummyLabel.*:3.molAtomMapNumber.2:5.dummyLabel.*:5.molAtomMapNumber.1|") RelabelMappedDummies(core, RGroupLabelling.Isotope) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R4:5.dummyLabel.R3|") # AtomMap, Isotope and MDLRGroup in, MDLRGroup out - AtomMap has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R4:5.dummyLabel.R3|") # AtomMap, Isotope and MDLRGroup in, MDLRGroup out - force Isotope priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, RGroupLabelling.Isotope) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R6:5.dummyLabel.R5|") # AtomMap, Isotope and MDLRGroup in, MDLRGroup out - force MDLRGroup priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, RGroupLabelling.MDLRGroup) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc(*)c(*)cn1 |atomProp:3.dummyLabel.R2:5.dummyLabel.R1|") # AtomMap, Isotope and MDLRGroup in, AtomMap out - AtomMap has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, outputLabels=RGroupLabelling.AtomMap) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([*:4])c([*:3])cn1 |atomProp:3.molAtomMapNumber.4:5.molAtomMapNumber.3|") # AtomMap, Isotope and MDLRGroup in, Isotope out - AtomMap has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, outputLabels=RGroupLabelling.Isotope) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([4*])c([3*])cn1") # AtomMap, Isotope and MDLRGroup in, AtomMap out - Isotope has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, inputLabels=(RGroupLabelling.Isotope | RGroupLabelling.MDLRGroup), outputLabels=RGroupLabelling.AtomMap) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([*:6])c([*:5])cn1 |atomProp:3.molAtomMapNumber.6:5.molAtomMapNumber.5|") # AtomMap, Isotope and MDLRGroup in, Isotope out - Isotope has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, inputLabels=(RGroupLabelling.Isotope | RGroupLabelling.MDLRGroup), outputLabels=RGroupLabelling.Isotope) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([6*])c([5*])cn1") # AtomMap, Isotope and MDLRGroup in, AtomMap out - MDLRGroup has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, inputLabels=RGroupLabelling.MDLRGroup, outputLabels=RGroupLabelling.AtomMap) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([*:2])c([*:1])cn1 |atomProp:3.molAtomMapNumber.2:5.molAtomMapNumber.1|") # AtomMap, Isotope and MDLRGroup in, Isotope out - MDLRGroup has priority core = Chem.Mol(allDifferentCore) RelabelMappedDummies(core, inputLabels=RGroupLabelling.MDLRGroup, outputLabels=RGroupLabelling.Isotope) self.assertEqual(Chem.MolToCXSmiles(core, p), "c1cc([2*])c([1*])cn1") def testRgroupMolZip(self): core = Chem.MolFromSmiles("CO") mols = [Chem.MolFromSmiles("C1NNO1")] rgroups, unmatched = RGroupDecompose(core, mols) for rgroup in rgroups: self.assertEqual(Chem.MolToSmiles(Chem.molzip(rgroup)), Chem.CanonSmiles("C1NNO1")) def testIncludeTargetMolInResults(self): core = Chem.MolFromSmiles("c1cc(-c2c([*:1])nn3nc([*:2])ccc23)nc(N(c2ccc([*:4])c([*:3])c2))n1") self.assertIsNotNone(core) mols = [Chem.MolFromSmiles(smi) for smi in [ "Cc1ccc2c(c3ccnc(Nc4cccc(c4)C(F)(F)F)n3)c(nn2n1)c5ccc(F)cc5", "Cc1ccc2c(c3ccnc(Nc4ccc(F)c(F)c4)n3)c(nn2n1)c5ccc(F)cc5", "Cc1ccc2c(c3ccnc(Nc4ccc5OCCOc5c4)n3)c(nn2n1)c6ccc(F)cc6", "Cc1ccc2c(c3ccnc(Nc4ccc(Cl)c(c4)C(F)(F)F)n3)c(nn2n1)c5ccc(F)cc5", "C1CC1c2nn3ncccc3c2c4ccnc(Nc5ccccc5)n4", "Fc1ccc(Nc2nccc(n2)c3c(nn4ncccc34)C5CC5)cc1F", "C1CCC(CC1)c2nn3ncccc3c2c4ccnc(Nc5ccccc5)n4", "Fc1ccc(Nc2nccc(n2)c3c(nn4ncccc34)C5CCCCC5)cc1F", "COCCOc1cnn2ncc(c3ccnc(Nc4cccc(OC)c4)n3)c2c1", "Cc1ccc2c(c3ccnc(Nc4ccc(F)c(F)c4)n3)c(nn2n1)c5ccccc5", "Cc1ccc2c(c3ccnc(Nc4ccc(Cl)c(c4)C(F)(F)F)n3)c(nn2n1)c5ccccc5", "Cc1ccc2c(c3ccnc(Nc4ccc5OCCOc5c4)n3)c(nn2n1)c6ccccc6", "Cc1ccc2c(c3ccnc(Nc4ccccc4)n3)c(nn2n1)c5cccc(c5)C(F)(F)F", "Cc1ccc2c(c3ccnc(Nc4ccc(F)c(F)c4)n3)c(nn2n1)c5cccc(c5)C(F)(F)F", "Cc1ccc2c(c3ccnc(Nc4ccc(Cl)c(c4)C(F)(F)F)n3)c(nn2n1)c5cccc(c5)C(F)(F)F", "Cc1ccc2c(c3ccnc(Nc4ccc5OCCOc5c4)n3)c(nn2n1)c6cccc(c6)C(F)(F)F", ]] self.assertTrue(all(mols)) ps = RGroupDecompositionParameters() ps.includeTargetMolInResults = True rgd = RGroupDecomposition(core, ps) for mol in mols: self.assertNotEqual(rgd.Add(mol), -1) self.assertTrue(rgd.Process()) def checkRow(row): targetMol = None # These are sets of int tuples rather just plain int tuples # because there can be cyclic R groups with 2 attachment points # in that case it is OK for 2 R groups to have exactly the same # target atom and bond indices allAtomIndices = set() allBondIndices = set() for rlabel, rgroup in row.items(): if rlabel == "Mol": targetMol = rgroup else: numNonRAtoms = len([atom for atom in rgroup.GetAtoms() if atom.GetAtomicNum() > 0 or not atom.GetAtomMapNum()]) self.assertGreater(rgroup.GetNumAtoms(), numNonRAtoms) numBonds = 0 if rlabel == "Core": numBonds = len([bond for bond in rgroup.GetBonds() if ( bond.GetBeginAtom().GetAtomicNum() > 0 or not bond.GetBeginAtom().GetAtomMapNum() ) and ( bond.GetEndAtom().GetAtomicNum() > 0 or not bond.GetEndAtom().GetAtomMapNum() )]) else: numBonds = rgroup.GetNumBonds() self.assertTrue(rgroup.HasProp("_rgroupTargetAtoms")) atomIndices = tuple(json.loads(rgroup.GetProp("_rgroupTargetAtoms"))) self.assertTrue(rgroup.HasProp("_rgroupTargetBonds")) bondIndices = tuple(json.loads(rgroup.GetProp("_rgroupTargetBonds"))) self.assertEqual(len(atomIndices), numNonRAtoms) allAtomIndices.add(atomIndices) self.assertEqual(len(bondIndices), numBonds) allBondIndices.add(bondIndices) self.assertIsNotNone(targetMol) flattenedAtomIndices = list(itertools.chain.from_iterable(allAtomIndices)) uniqueAtomIndices = set(flattenedAtomIndices) self.assertEqual(len(flattenedAtomIndices), len(uniqueAtomIndices)) self.assertEqual(len(flattenedAtomIndices), targetMol.GetNumAtoms()) flattenedBondIndices = list(itertools.chain.from_iterable(allBondIndices)) uniqueBondIndices = set(flattenedBondIndices) self.assertEqual(len(flattenedBondIndices), len(uniqueBondIndices)) self.assertEqual(len(flattenedBondIndices), targetMol.GetNumBonds()) rows = rgd.GetRGroupsAsRows() self.assertEqual(len(rows), len(mols)) for row in rows: checkRow(row) cols = rgd.GetRGroupsAsColumns() rows = [] for i in range(len(mols)): row = {} for rlabel, rgroups in cols.items(): self.assertEqual(len(rgroups), len(mols)) row[rlabel] = rgroups[i] rows.append(row) self.assertEqual(len(rows), len(mols)) for row in rows: checkRow(row) if __name__ == '__main__': rdBase.DisableLog("rdApp.debug") unittest.main()