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|
import copy
import math
import os
import pickle
import unittest
import numpy
import rdkit.DistanceGeometry as DG
from rdkit import Chem, RDConfig, rdBase
from rdkit.Chem import AllChem, ChemicalForceFields, rdDistGeom, rdMolAlign
from rdkit.Geometry import ComputeSignedDihedralAngle
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 = [
116.330, 106.246, 109.816, 104.890, 93.060, 140.803, 139.253, 95.820, 123.591, 108.655
]
nenergies = []
for cid in cids:
ff = ChemicalForceFields.UFFGetMoleculeForceField(mol, 10.0, cid)
ee = ff.CalcEnergy()
nenergies.append(ee)
# print(['%.3f' % 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 = [3, 2, 7, 6, 3, 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)]
# print(nconfs)
self.assertTrue(max(d) <= 1)
# previous settings
params = rdDistGeom.ETKDG()
params.randomSeed = 100
params.maxIterations = 30
params.pruneRmsThresh = 1.5
params.useSymmetryForPruning = False
nconfs = []
expected = [4, 5, 5, 6, 7, 3]
for smi in smiles:
mol = Chem.MolFromSmiles(smi)
cids = rdDistGeom.EmbedMultipleConfs(mol, 50, params)
nconfs.append(len(cids))
d = [abs(x - y) for x, y in zip(expected, nconfs)]
# print(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 = 3.0
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.assertEqual(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
# as large as we can go without overflowing since 11 * 195225786 should not overflow the int
self.assertDeterministicWithSeed(195225786)
self.assertDeterministicWithSeed(195225787) # one higher seed will overflow though
# another large seeds that shouldn't overflow internals and make them non-deterministic
self.assertDeterministicWithSeed(0x1CEB00DA)
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)
def testProvidingBoundsMatrix(self):
m1 = Chem.MolFromSmiles("C1CCC1C")
bm1 = rdDistGeom.GetMoleculeBoundsMatrix(m1)
bm1[0, 3] = 1.21
bm1[3, 0] = 1.20
bm1[2, 3] = 1.21
bm1[3, 2] = 1.20
bm1[4, 3] = 1.21
bm1[3, 4] = 1.20
DG.DoTriangleSmoothing(bm1)
ps = rdDistGeom.EmbedParameters()
ps.useRandomCoords = True
ps.SetBoundsMat(bm1)
ps.randomSeed = 0xf00d
self.assertEqual(rdDistGeom.EmbedMolecule(m1, ps), 0)
conf = m1.GetConformer()
self.assertAlmostEqual((conf.GetAtomPosition(3) - conf.GetAtomPosition(0)).Length(), 1.2,
delta=0.05)
self.assertAlmostEqual((conf.GetAtomPosition(3) - conf.GetAtomPosition(2)).Length(), 1.2,
delta=0.05)
self.assertAlmostEqual((conf.GetAtomPosition(3) - conf.GetAtomPosition(4)).Length(), 1.2,
delta=0.05)
def testProvidingCPCI(self):
"""
test for a ring molecule, repeated generating a conformer with and without enforcing
an additional +ve interaction between a pair of non-bonded atoms (termed CPCI,
custom pairwise charge-like interaciton), in every iteration, applying CPCI should
yield a conformer where this pair of atoms are further apart.
"""
for i in range(5):
ps = rdDistGeom.EmbedParameters()
ps.randomSeed = i
ps.useBasicKnowledge = True
ps.useRandomCoords = False
m1 = Chem.MolFromSmiles("C1CCCC1C")
self.assertEqual(rdDistGeom.EmbedMolecule(m1, ps), 0)
m2 = Chem.MolFromSmiles("C1CCCC1C")
ps = rdDistGeom.EmbedParameters()
ps.randomSeed = i
ps.useRandomCoords = False
ps.useBasicKnowledge = True
ps.SetCPCI({(0, 3): 0.9})
self.assertEqual(rdDistGeom.EmbedMolecule(m2, ps), 0)
conf1 = m1.GetConformer()
conf2 = m2.GetConformer()
self.assertTrue((conf2.GetAtomPosition(3) -
conf2.GetAtomPosition(0)).Length() > (conf1.GetAtomPosition(3) -
conf1.GetAtomPosition(0)).Length())
def testScaleBoundsMatForce(self):
"""
for pentane, set a target distance for the 1-5 distance, and generate conformers with changing weights for (all) the atom pair distance restraints,
the conformer with the stronger weight for the atom pairs will always have a 1-5 distance closer to the target value than that with the weaker weight.
"""
target = 4
for i in range(5):
ps = rdDistGeom.EmbedParameters()
ps.randomSeed = i
ps.useBasicKnowledge = True
ps.useRandomCoords = False
m1 = Chem.MolFromSmiles("CCCCC")
bm1 = rdDistGeom.GetMoleculeBoundsMatrix(m1)
bm1[0, 4] = target
bm1[4, 0] = target
DG.DoTriangleSmoothing(bm1)
ps.boundsMatForceScaling = 0.1
ps.SetBoundsMat(bm1)
self.assertEqual(rdDistGeom.EmbedMolecule(m1, ps), 0)
m2 = Chem.MolFromSmiles("CCCCC")
ps = rdDistGeom.EmbedParameters()
ps.randomSeed = i
ps.useBasicKnowledge = True
ps.useRandomCoords = False
ps.boundsMatForceScaling = 10
ps.SetBoundsMat(bm1)
self.assertEqual(rdDistGeom.EmbedMolecule(m2, ps), 0)
conf1 = m1.GetConformer()
conf2 = m2.GetConformer()
self.assertTrue(
abs((conf2.GetAtomPosition(4) - conf2.GetAtomPosition(0)).Length() -
target) < abs((conf1.GetAtomPosition(4) - conf1.GetAtomPosition(0)).Length() - target))
def testETKDGv3amide(self):
"""
test for a macrocycle molecule, ETKDGv3 samples trans amide
"""
def get_atom_mapping(mol, smirks="[O:1]=[C:2]@;-[NX3:3]-[H:4]"):
qmol = Chem.MolFromSmarts(smirks)
ind_map = {}
for atom in qmol.GetAtoms():
map_num = atom.GetAtomMapNum()
if map_num:
ind_map[map_num - 1] = atom.GetIdx()
map_list = [ind_map[x] for x in sorted(ind_map)]
matches = list()
for match in mol.GetSubstructMatches(qmol, uniquify=False):
mas = [match[x] for x in map_list]
matches.append(tuple(mas))
return matches
smiles = "C1CCC(=O)NCCCCCC(=O)NC1"
smiles_mol = Chem.MolFromSmiles(smiles)
mol = Chem.AddHs(smiles_mol)
params = AllChem.ETKDGv3()
params.randomSeed = 0
AllChem.EmbedMolecule(mol, params)
conf = mol.GetConformer(0)
for torsion in get_atom_mapping(mol):
a1, a2, a3, a4 = [conf.GetAtomPosition(i) for i in torsion]
self.assertAlmostEqual(abs(ComputeSignedDihedralAngle(a1, a2, a3, a4)), 3.14, delta=0.1)
def testGetTorsionBonds(self):
m = Chem.AddHs(Chem.MolFromSmiles('CCCC'))
ts = rdDistGeom.GetExperimentalTorsions(m)
self.assertEqual(len(ts), 1)
self.assertEqual(ts[0]["bondIndex"], 1)
self.assertEqual(ts[0]["torsionIndex"], 229)
self.assertEqual(ts[0]["smarts"], '[!#1:1][CX4H2:2]!@;-[CX4H2:3][!#1:4]')
self.assertEqual(list(ts[0]["V"]), [0.0, 0.0, 4.0, 0.0, 0.0, 0.0])
self.assertEqual(list(ts[0]["signs"]), [1, 1, 1, 1, 1, 1])
self.assertEqual(list(ts[0]["atomIndices"]), [0, 1, 2, 3])
params = rdDistGeom.ETKDGv3()
ts = rdDistGeom.GetExperimentalTorsions(m, params)
self.assertEqual(len(ts), 1)
self.assertEqual(ts[0]["bondIndex"], 1)
self.assertEqual(ts[0]["smarts"], '[!#1:1][CX4H2:2]!@;-[CX4H2:3][!#1:4]')
self.assertEqual(ts[0]["torsionIndex"], 229)
self.assertEqual(list(ts[0]["V"]), [0.0, 0.0, 4.0, 0.0, 0.0, 0.0])
self.assertEqual(list(ts[0]["signs"]), [1, 1, 1, 1, 1, 1])
self.assertEqual(list(ts[0]["atomIndices"]), [0, 1, 2, 3])
def testTrackFailures(self):
params = AllChem.ETKDGv3()
params.trackFailures = True
params.maxIterations = 50
params.randomSeed = 42
mol = Chem.MolFromSmiles('C=CC1=C(N)Oc2cc1c(-c1cc(C(C)O)cc(=O)cc1C1NCC(=O)N1)c(OC)c2OC')
mol = Chem.AddHs(mol)
AllChem.EmbedMolecule(mol, params)
cnts = params.GetFailureCounts()
self.assertGreater(cnts[AllChem.EmbedFailureCauses.INITIAL_COORDS], 5)
self.assertGreater(cnts[AllChem.EmbedFailureCauses.ETK_MINIMIZATION], 10)
def testCoordMap(self):
mol = Chem.AddHs(Chem.MolFromSmiles("OCCC"))
ps = rdDistGeom.EmbedParameters()
coordMap = {0: geom.Point3D(0, 0, 0), \
1: geom.Point3D(0, 0, 1.5),
2: geom.Point3D(0, 1.5, 1.5)
}
ps.SetCoordMap(coordMap)
ps.randomSeed = 42
rdDistGeom.EmbedMolecule(mol, ps)
conf = mol.GetConformer()
v1 = conf.GetAtomPosition(0) - conf.GetAtomPosition(1)
v2 = conf.GetAtomPosition(2) - conf.GetAtomPosition(1)
angle = v1.AngleTo(v2)
self.assertAlmostEqual(angle, math.pi / 2.0, delta=0.15)
# make sure that we can call that a second time
coordMap = {0: geom.Point3D(0, 0, 0), \
1: geom.Point3D(1.5, 0, 0),
2: geom.Point3D(1.5, 1.5, 0)
}
ps.SetCoordMap(coordMap)
ps.randomSeed = 42
rdDistGeom.EmbedMolecule(mol, ps)
conf = mol.GetConformer()
v1 = conf.GetAtomPosition(0) - conf.GetAtomPosition(1)
v2 = conf.GetAtomPosition(2) - conf.GetAtomPosition(1)
angle = v1.AngleTo(v2)
self.assertAlmostEqual(angle, math.pi / 2.0, delta=0.15)
def testSymmetrizeTerminal(self):
mol = Chem.AddHs(Chem.MolFromSmiles("FCC(=O)O"))
ps = rdDistGeom.ETKDGv3()
ps.randomSeed = 0xc0ffee
ps.pruneRmsThresh = 0.5
cids = rdDistGeom.EmbedMultipleConfs(mol, 50, ps)
self.assertEqual(len(cids), 1)
ps.symmetrizeConjugatedTerminalGroupsForPruning = False
cids = rdDistGeom.EmbedMultipleConfs(mol, 50, ps)
self.assertGreater(len(cids), 1)
if __name__ == '__main__':
unittest.main()
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