from __future__ import print_function import unittest import os, copy import math import numpy from rdkit.six.moves import cPickle as pickle from rdkit.six import next from rdkit import Chem from rdkit.Chem import AllChem from rdkit.Chem import rdDistGeom, ChemicalForceFields, rdMolAlign from rdkit import RDConfig, rdBase from rdkit.Geometry import rdGeometry as geom from rdkit.RDLogger import logger logger = logger() def feq(v1, v2, tol=1.e-4): return abs(v1 - v2) < tol def lstEq(l1, l2, tol=1.0e-4): ln = len(l1) if (ln != len(l2)): return 0 for i in range(ln): if abs(l1[i] - l2[i]) > tol: return 0 return 1 def compareWithOld(smilesFile, sdFile): smiSup = Chem.SmilesMolSupplier(smilesFile, ",", 0, -1) sdsup = Chem.SDMolSupplier(sdFile) im = 0 for mol in smiSup: cid = rdDistGeom.EmbedMolecule(mol, 10, 1) omol = sdsup[im] assert cid == 0 conf = mol.GetConformer(0) oconf = omol.GetConformer() nat = mol.GetNumAtoms() for i in range(nat): #atm = mol.GetAtomWithIdx(i) #oatm = omol.GetAtomWithIdx(i) pos = conf.GetAtomPosition(i) opos = oconf.GetAtomPosition(i) if not lstEq(pos, opos): return 0 im += 1 return 1 def compareMatrices(bm1, bm2, map, tol=1.0e-5): N = numpy.shape(bm1)[0] for i in range(1, N): for j in range(i): l, m = map[i], map[j] if (l < m): l, m = m, l if (abs(bm1[l, m] - bm2[i, j]) > tol): return 0 if (abs(bm1[m, l] - bm2[j, i]) > tol): return 0 return 1 def compareOrder(smi1, smi2, tol=1.0e-5): m1 = Chem.MolFromSmiles(smi1) m2 = Chem.MolFromSmiles(smi2) bm1 = rdDistGeom.GetMoleculeBoundsMatrix(m1) bm2 = rdDistGeom.GetMoleculeBoundsMatrix(m2) map = m1.GetSubstructMatch(m2) return compareMatrices(bm1, bm2, map, tol) def computeDist(lst1, lst2): res = 0.0 for i, val in enumerate(lst1): res += (val - lst2[i]) * (val - lst2[i]) res = math.sqrt(res) return res def computeChiralVol(pt1, pt2, pt3, pt4): v1 = pt1 - pt4 v2 = pt2 - pt4 v3 = pt3 - pt4 cp = v2.CrossProduct(v3) vol = v1.DotProduct(cp) return vol class TestCase(unittest.TestCase): def setUp(self): pass def _test0Cdk2(self): fileN = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'cis_trans_cases.csv') ofile = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'embedDistOpti.sdf') self.assertTrue(compareWithOld(fileN, ofile)) def test1Small(self): #writer = Chem.SDWriter("test.sdf") # single double and tripple atoms cases should not fail mol = Chem.MolFromSmiles('O') rdDistGeom.EmbedMolecule(mol, 10, 1) conf = mol.GetConformer() self.assertTrue(lstEq(conf.GetAtomPosition(0), [0.0, 0.0, 0.0])) #writer.write(mol) mol = Chem.MolFromSmiles('CO') rdDistGeom.EmbedMolecule(mol, 10, 1) conf = mol.GetConformer() self.assertTrue(lstEq(conf.GetAtomPosition(0), [0.69192, 0.0, 0.0])) self.assertTrue(lstEq(conf.GetAtomPosition(1), [-0.69192, 0.0, 0.0])) #writer.write(mol) mol = Chem.MolFromSmiles('CCC') rdDistGeom.EmbedMolecule(mol, 10, 1) conf = mol.GetConformer() self.assertTrue(lstEq(conf.GetAtomPosition(0), [-1.21676, -0.2989, 0.0])) self.assertTrue(lstEq(conf.GetAtomPosition(1), [-0.00604, 0.59337, 0.0])) self.assertTrue(lstEq(conf.GetAtomPosition(2), [1.22281, -0.29446, 0.0])) #writer.write(mol) mol = Chem.MolFromSmiles('O=C=O') rdDistGeom.EmbedMolecule(mol, 10, 1) conf = mol.GetConformer() #writer.write(mol) self.assertTrue(lstEq(conf.GetAtomPosition(0), [-1.2180, -0.06088, 0.0])) self.assertTrue(lstEq(conf.GetAtomPosition(1), [-0.00408, 0.12116, 0.0])) self.assertTrue(lstEq(conf.GetAtomPosition(2), [1.22207, -0.060276, 0.0])) mol = Chem.MolFromSmiles('C=C=C=C') rdDistGeom.EmbedMolecule(mol, 10, 1, useExpTorsionAnglePrefs=False, useBasicKnowledge=False) conf = mol.GetConformer() #writer.write(mol) d1 = computeDist(conf.GetAtomPosition(0), conf.GetAtomPosition(1)) self.assertTrue(feq(d1, 1.31, 0.01)) d2 = computeDist(conf.GetAtomPosition(0), conf.GetAtomPosition(2)) self.assertTrue(feq(d2, 2.59, 0.05)) d3 = computeDist(conf.GetAtomPosition(0), conf.GetAtomPosition(3)) self.assertTrue(feq(d3, 3.84, 0.1)) d4 = computeDist(conf.GetAtomPosition(1), conf.GetAtomPosition(2)) self.assertTrue(feq(d4, 1.29, 0.01)) d5 = computeDist(conf.GetAtomPosition(1), conf.GetAtomPosition(3)) self.assertTrue(feq(d5, 2.54, 0.1)) d6 = computeDist(conf.GetAtomPosition(2), conf.GetAtomPosition(3)) self.assertTrue(feq(d6, 1.31, 0.01)) def test2Utils(self): mol = Chem.MolFromSmiles('CC') bm = rdDistGeom.GetMoleculeBoundsMatrix(mol) self.assertTrue(bm[1, 0] > 0) self.assertTrue(bm[0, 1] > 0) self.assertTrue(bm[0, 1] >= bm[1, 0]) self.assertTrue(bm[1, 0] < 1.510) self.assertTrue(bm[0, 1] > 1.510) def test3MultiConf(self): mol = Chem.MolFromSmiles("CC(C)(C)c(cc12)n[n]2C(=O)/C=C(N1)/COC") cids = rdDistGeom.EmbedMultipleConfs(mol, 10, maxAttempts=30, randomSeed=100, useExpTorsionAnglePrefs=False, useBasicKnowledge=False) energies = [112.98, 103.57, 110.78, 100.40, 95.37, 101.64, 114.72, 112.65, 124.53, 107.50] nenergies = [] for cid in cids: ff = ChemicalForceFields.UFFGetMoleculeForceField(mol, 10.0, cid) ee = ff.CalcEnergy() nenergies.append(ee) #print(['%.2f'%x for x in nenergies]) #print(nenergies) self.assertTrue(lstEq(energies, nenergies, tol=1e-2)) def test4OrderDependence(self): self.assertTrue( compareOrder("CC(C)(C)C(=O)NC(C1)CC(N2C)CCC12", "CN1C2CCC1CC(NC(=O)C(C)(C)C)C2")) #issue 230 self.assertTrue(compareOrder("C#CC(C)(C)N(CN1)C\\N=C/1SC", "CSC1=NCN(C(C)(C)C#C)CN1")) #issue 232 self.assertTrue( compareOrder("CC(C)(C)C(=O)NC(C1)CC(N2C)CCC12", "CN1C2CCC1CC(NC(=O)C(C)(C)C)C2")) def test5Issue285(self): m = Chem.MolFromSmiles('CNC=O') cs = rdDistGeom.EmbedMultipleConfs(m, 10) for i, ci in enumerate(cs): for j in range(i + 1, len(cs)): cj = cs[j] self.assertTrue(Chem.MolToMolBlock(m, confId=ci) != Chem.MolToMolBlock(m, confId=cj)) def test6RmsPruning(self): smiles = [ 'CC(C)CC(NC(C1[N+]CCC1)=O)C([O-])=O', 'CC(NC(CO)C(O)c1ccc([N+]([O-])=O)cc1)=O', 'CC([N+])C(NC(C)C(N1C(C=O)CCC1)=O)=O', 'CC(NC1C(O)C=C(C([O-])=O)OC1C(O)C(O)CO)=O', 'CCCC=C(NC(C1CC1(C)C)=O)C([O-])=O', 'OCC(O)C(O)C(Cn1c2c(cc(C)c(C)c2)nc-2c(=O)[nH]c(=O)nc12)O' ] nconfs = [] expected = [5, 6, 6, 6, 6, 3] for smi in smiles: mol = Chem.MolFromSmiles(smi) cids = rdDistGeom.EmbedMultipleConfs(mol, 50, maxAttempts=30, randomSeed=100, pruneRmsThresh=1.5) nconfs.append(len(cids)) d = [abs(x - y) for x, y in zip(expected, nconfs)] self.assertTrue(max(d) <= 1) def test6Chirality(self): # turn on chirality and we should get chiral volume that is pretty consistent and # positive tgtVol = 13.0 smiles = "Cl[C@](C)(F)Br" mol = Chem.MolFromSmiles(smiles) cids = rdDistGeom.EmbedMultipleConfs(mol, 30, maxAttempts=30, randomSeed=100) self.assertTrue(len(cids) == 30) for cid in cids: conf = mol.GetConformer(cid) vol = computeChiralVol( conf.GetAtomPosition(0), conf.GetAtomPosition(2), conf.GetAtomPosition(3), conf.GetAtomPosition(4)) self.assertTrue(abs(vol - tgtVol) < 1) # turn of chirality and now we should see both chiral forms smiles = "ClC(C)(F)Br" mol = Chem.MolFromSmiles(smiles) cids = rdDistGeom.EmbedMultipleConfs(mol, 30, maxAttempts=30, randomSeed=120) self.assertTrue(len(cids) == 30) nPos = 0 nNeg = 0 for cid in cids: conf = mol.GetConformer(cid) vol = computeChiralVol( conf.GetAtomPosition(0), conf.GetAtomPosition(2), conf.GetAtomPosition(3), conf.GetAtomPosition(4)) self.assertTrue(abs(vol - tgtVol) < 1 or abs(vol + tgtVol) < 1) if vol < 0: nNeg += 1 else: nPos += 1 self.assertTrue(nPos > 0) self.assertTrue(nNeg > 0) tgtVol = 5.0 for i in range(10): smiles = "Cl[C@H](F)Br" mol = Chem.MolFromSmiles(smiles) ci = rdDistGeom.EmbedMolecule(mol, 30, (i + 1) * 10) conf = mol.GetConformer(ci) vol = computeChiralVol( conf.GetAtomPosition(0), conf.GetAtomPosition(1), conf.GetAtomPosition(2), conf.GetAtomPosition(3)) self.assertTrue(abs(vol - tgtVol) < 1, "%s %s" % (vol, tgtVol)) tgtVol = 3.5 expected = [-3.62, -3.67, -3.72, 3.91, 3.95, 3.98, 3.90, 3.94, 3.98, 3.91] nPos = 0 nNeg = 0 for i in range(30): smiles = "ClC(F)Br" mol = Chem.MolFromSmiles(smiles) ci = rdDistGeom.EmbedMolecule(mol, 30, (i + 1) * 10) conf = mol.GetConformer(ci) vol = computeChiralVol( conf.GetAtomPosition(0), conf.GetAtomPosition(1), conf.GetAtomPosition(2), conf.GetAtomPosition(3)) self.assertTrue(abs(vol - tgtVol) < 1 or abs(vol + tgtVol) < 1) if vol < 0: nNeg += 1 else: nPos += 1 self.assertTrue(nPos > 0) self.assertTrue(nNeg > 0) smiles = "Cl[C@H](F)Br" m = Chem.MolFromSmiles(smiles) mol = Chem.AddHs(m) cids = rdDistGeom.EmbedMultipleConfs(mol, 10, maxAttempts=30, randomSeed=100) self.assertTrue(len(cids) == 10) tgtVol = 10.5 for cid in cids: conf = mol.GetConformer(cid) vol = computeChiralVol( conf.GetAtomPosition(0), conf.GetAtomPosition(2), conf.GetAtomPosition(3), conf.GetAtomPosition(4)) self.assertTrue(abs(vol - tgtVol) < 2.) # let's try a little more complicated system expectedV1 = -2.0 expectedV2 = -2.9 for i in range(5): smi = "C1=CC=C(C=C1)[C@H](OC1=C[NH]N=C1)C(=O)[NH]C[C@H](Cl)C1=CC=NC=C1" mol = Chem.MolFromSmiles(smi) ci = rdDistGeom.EmbedMolecule(mol, randomSeed=(i + 1) * 15) self.assertTrue(ci >= 0) ff = ChemicalForceFields.UFFGetMoleculeForceField(mol, 10.0, ci) ff.Minimize() conf = mol.GetConformer(ci) vol1 = computeChiralVol( conf.GetAtomPosition(6), conf.GetAtomPosition(3), conf.GetAtomPosition(7), conf.GetAtomPosition(13)) self.assertTrue(abs(vol1 - expectedV1) < 1 or abs(vol1 + expectedV1) < 1) if vol1 < 0: nNeg += 1 else: nPos += 1 vol2 = computeChiralVol( conf.GetAtomPosition(17), conf.GetAtomPosition(16), conf.GetAtomPosition(18), conf.GetAtomPosition(19)) self.assertTrue(abs(vol2 - expectedV2) < 1 or abs(vol2 + expectedV2) < 1) # remove the chiral specification and we should see other chiral # forms of the compound expectedV1 = 2.0 #[-2.30, -2.31, -2.30, 2.30, -1.77] expectedV2 = 2.8 #[2.90, 2.89, 2.69, -2.90, -2.93] self.assertTrue(nPos > 0) self.assertTrue(nNeg > 0) for i in range(5): smi = "C1=CC=C(C=C1)C(OC1=C[NH]N=C1)C(=O)[NH]CC(Cl)C1=CC=NC=C1" mol = Chem.MolFromSmiles(smi) ci = rdDistGeom.EmbedMolecule(mol, 30, (i + 1) * 10) ff = ChemicalForceFields.UFFGetMoleculeForceField(mol, 10.0, ci) ff.Minimize() conf = mol.GetConformer(ci) vol1 = computeChiralVol( conf.GetAtomPosition(6), conf.GetAtomPosition(3), conf.GetAtomPosition(7), conf.GetAtomPosition(13)) vol2 = computeChiralVol( conf.GetAtomPosition(17), conf.GetAtomPosition(16), conf.GetAtomPosition(18), conf.GetAtomPosition(19)) self.assertTrue(abs(abs(vol1) - expectedV1) < 1.0) self.assertTrue(abs(abs(vol2) - expectedV2) < 1.0) def test7ConstrainedEmbedding(self): ofile = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'constrain1.sdf') suppl = Chem.SDMolSupplier(ofile) ref = next(suppl) probe = copy.deepcopy(ref) cMap = {} for i in range(5): cMap[i] = ref.GetConformer().GetAtomPosition(i) ci = rdDistGeom.EmbedMolecule(probe, coordMap=cMap, randomSeed=23) self.assertTrue(ci > -1) algMap = list(zip(range(5), range(5))) ssd = rdMolAlign.AlignMol(probe, ref, atomMap=algMap) self.assertTrue(ssd < 0.1) def test8MultiThreadMultiConf(self): if (rdBase.rdkitBuild.split('|')[2] != "MINGW"): ENERGY_TOLERANCE = 1.0e-6 MSD_TOLERANCE = 1.0e-6 else: ENERGY_TOLERANCE = 1.0 MSD_TOLERANCE = 1.0e-5 mol = Chem.AddHs(Chem.MolFromSmiles("CC(C)(C)c(cc12)n[n]2C(=O)/C=C(N1)/COC")) cids = rdDistGeom.EmbedMultipleConfs(mol, 200, maxAttempts=30, randomSeed=100) energies = [] for cid in cids: ff = ChemicalForceFields.UFFGetMoleculeForceField(mol, 10.0, cid) ee = ff.CalcEnergy() energies.append(ee) mol2 = Chem.AddHs(Chem.MolFromSmiles("CC(C)(C)c(cc12)n[n]2C(=O)/C=C(N1)/COC")) cids2 = rdDistGeom.EmbedMultipleConfs(mol2, 200, maxAttempts=30, randomSeed=100, numThreads=4) self.assertTrue(lstEq(cids, cids2)) nenergies = [] for cid in cids2: ff = ChemicalForceFields.UFFGetMoleculeForceField(mol2, 10.0, cid) ee = ff.CalcEnergy() nenergies.append(ee) self.assertTrue(lstEq(energies, nenergies, tol=ENERGY_TOLERANCE)) for cid in cids: msd = 0.0 for i in range(mol.GetNumAtoms()): msd += (mol.GetConformer().GetAtomPosition(i) \ - mol2.GetConformer().GetAtomPosition(i)).LengthSq() msd /= mol.GetNumAtoms() self.assertTrue(msd < MSD_TOLERANCE) def _compareConfs(self, mol, ref, molConfId, refConfId): self.assertEqual(mol.GetNumAtoms(), ref.GetNumAtoms()) molConf = mol.GetConformer(molConfId) refConf = ref.GetConformer(refConfId) for i in range(mol.GetNumAtoms()): mp = molConf.GetAtomPosition(i) rp = refConf.GetAtomPosition(i) self.assertAlmostEqual((mp - rp).Length(), 0.0, 3) def test9EmbedParams(self): mol = Chem.AddHs(Chem.MolFromSmiles('OCCC')) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'simple_torsion.dg.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) params = rdDistGeom.EmbedParameters() params.randomSeed = 42 self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'simple_torsion.etdg.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) params = rdDistGeom.EmbedParameters() params.randomSeed = 42 params.useExpTorsionAnglePrefs = True self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) params = rdDistGeom.ETDG() params.randomSeed = 42 self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'simple_torsion.etkdg.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) params = rdDistGeom.EmbedParameters() params.randomSeed = 42 params.useExpTorsionAnglePrefs = True params.useBasicKnowledge = True self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) params = rdDistGeom.ETKDG() params.randomSeed = 42 self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'simple_torsion.kdg.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) params = rdDistGeom.EmbedParameters() params.randomSeed = 42 params.useBasicKnowledge = True self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) params = rdDistGeom.KDG() params.randomSeed = 42 self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) def test10ETKDGv2(self): mol = Chem.AddHs(Chem.MolFromSmiles('n1cccc(C)c1ON')) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'torsion.etkdg.v2.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) params = rdDistGeom.ETKDGv2() params.randomSeed = 42 self.assertEqual(rdDistGeom.EmbedMolecule(mol, params), 0) self._compareConfs(mol, ref, 0, 0) def assertDeterministicWithSeed(self, seed): input_mol = Chem.MolFromSmiles('CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc1') params = AllChem.ETKDG() params.pruneRmsThresh = -1.0 # skip internal RMSD pruning if seed is not None: params.randomSeed = seed firstMol = Chem.AddHs(input_mol) firstIds = AllChem.EmbedMultipleConfs(firstMol, 11, params) secondMol = Chem.AddHs(input_mol) secondIds = AllChem.EmbedMultipleConfs(secondMol, 11, params) self.assertEqual(list(firstIds), list(secondIds)) self.assertEqual(firstMol.GetNumConformers(), secondMol.GetNumConformers()) nonDeterministic = False for confIdx in range(firstMol.GetNumConformers()): firstConf = firstMol.GetConformer(confIdx) secondConf = secondMol.GetConformer(confIdx) firstPositions = firstConf.GetPositions() secondPositions = secondConf.GetPositions() d = firstPositions - secondPositions rmsd = numpy.sqrt(numpy.sum(d * d)) if seed >= 0: self.assertEquals(rmsd, 0.0) elif rmsd != 0.0: nonDeterministic = True if seed < 0: self.assertTrue(nonDeterministic) def testETKDGIsDeterministic(self): self.assertDeterministicWithSeed(-1) # not deterministic self.assertDeterministicWithSeed(0) # deterministic self.assertDeterministicWithSeed(1) # deterministic self.assertDeterministicWithSeed(195225786) # as large as we can go without overflowing since 11 * 195225786 should not overflow the int self.assertDeterministicWithSeed(195225787) # one higher seed will overflow though self.assertDeterministicWithSeed(0x1CEB00DA) # another large seeds that shouldn't overflow internals and make them non-deterministic def testGithub1763(self): mol = Chem.MolFromSmiles('CCCCC') bm1 = rdDistGeom.GetMoleculeBoundsMatrix(mol) bm2 = rdDistGeom.GetMoleculeBoundsMatrix(mol,doTriangleSmoothing=False) self.assertTrue(bm1[0, 4] < bm2[0,4]) def testGithub2057(self): # ensure that ETKDG is the default Embedder mol = Chem.AddHs(Chem.MolFromSmiles('OCCC')) fn = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol', 'DistGeomHelpers', 'test_data', 'simple_torsion.etkdg.mol') ref = Chem.MolFromMolFile(fn, removeHs=False) self.assertEqual(rdDistGeom.EmbedMolecule(mol, randomSeed=42), 0) self._compareConfs(mol, ref, 0, 0) if __name__ == '__main__': unittest.main()