def testdetect_from_ligand_ensemble(self):
wrk_dir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand_ensemble"
with PushDir(wrk_dir):
test_overlay = io.MoleculeReader("test_overlay.mol2")
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"ring_planar_projected"
]
ligand_pharmacophore.detect_from_ligand_ensemble(
ligands=test_overlay, cutoff=2)
# ligand_pharmacophore.pymol_visulisation(outdir="")
self.assertEqual(2, len(ligand_pharmacophore.detected_features))
def testdetect_from_ligand(self):
wrkdir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand"
with PushDir(wrkdir):
self.ligand_pharmacophore.feature_definitions = ["acceptor"]
print(self.ligand_pharmacophore.feature_definitions["acceptor"].
point_generator_names)
self.ligand_pharmacophore.detect_from_ligand(ligand=self.crystal)
self.assertEqual(5,
len(self.ligand_pharmacophore.detected_features))
# test score setter
self.assertEqual(
0, self.ligand_pharmacophore.detected_features[0].score)
self.ligand_pharmacophore.detected_features[0].score = 5
self.assertEqual(
5, self.ligand_pharmacophore.detected_features[0].score)
# test write
for f in self.ligand_pharmacophore.detected_features:
self.ligand_pharmacophore.add_feature(f)
self.ligand_pharmacophore.write(
pharmacophore_path="pharmacophore.cm")
read_me = LigandPharmacophoreModel.from_file("pharmacophore.cm")
self.assertEqual(len(self.ligand_pharmacophore.features),
len(read_me.features))
print(read_me.features[0].spheres[0].centre)
def create_multiple_pharmacophore_files():
# setting output directory
out_dir = "testdata/pharmacophore_extension/PharmacophoreModel"
if not os.path.exists(out_dir):
os.mkdir(out_dir)
# create files
mols = io.CrystalReader(
"testdata/pharmacophore_extension/provided_data/test_overlay.mol2")
for mol in mols:
lp = LigandPharmacophoreModel()
lp.feature_definitions = ["ring_planar_projected"]
lp.detect_from_ligand(mol)
for feature in lp.detected_features:
lp.add_feature(feature)
lp.write(os.path.join(out_dir, f"{mol.identifier}.cm"))
def testdetect_from_ligand_ensemble_cdk2(self):
wrk_dir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand_ensemble_big_all"
with PushDir(wrk_dir):
test_overlay = io.MoleculeReader("cdk2_ligands.mol2")
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"ring_planar_projected", "donor_projected",
"acceptor_projected"
]
ligand_pharmacophore.detect_from_ligand_ensemble(
ligands=test_overlay, cutoff=2)
feature_count = 4
selected = ligand_pharmacophore.top_features(num=feature_count)
ligand_pharmacophore.detected_features = selected
self.assertEqual(feature_count, len(ligand_pharmacophore))
def generate_pharmacophore(ligands, ref_pdb, out_dir):
lig_pharms = []
for ligand in ligands:
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"ring", "acceptor_projected", "donor_projected"
]
ligand_pharmacophore.detect_from_ligand(ligand)
for feat in ligand_pharmacophore.detected_features:
ligand_pharmacophore.add_feature(feat)
lig_pharms.append(ligand_pharmacophore)
# 20 %
cutoff = len(ligands) * 0.2
feats, feat_point_grds = create_consensus(lig_pharms, cutoff=cutoff)
print(feats)
for feat in feats:
if feat.identifier == "ring":
p = feat.spheres[0].centre
feat.spheres = (GeometricDescriptors.Sphere((p[0], p[1], p[2]),
2.0), )
feat.point = feat.spheres[0]
ensemble_pharm = LigandPharmacophoreModel()
ensemble_pharm.detected_features = feats
ensemble_pharm.feature_point_grids = feat_point_grds
ensemble_pharm.ligands = ligands
ensemble_pharm.detected_features = ensemble_pharm.top_features(num=6)
pymol_o = os.path.join(out_dir, "pymol")
if not os.path.exists(pymol_o):
os.mkdir(pymol_o)
ensemble_pharm.pymol_visulisation(pymol_o)
# enable rescoring
tmp = tempfile.mkdtemp()
ftp_download([ref_pdb, tmp])
hr = Results(super_grids={
"apolar": feat_point_grds["ring"],
"donor": feat_point_grds["donor_projected"],
"acceptor": feat_point_grds["acceptor_projected"]
},
protein=Protein.from_file(
os.path.join(tmp, f"{ref_pdb}.pdb")))
hr_out = os.path.join(out_dir, "hr")
if not os.path.exists(hr_out):
os.mkdir(hr_out)
with HotspotWriter(hr_out) as w:
w.write(hr)
p_out = os.path.join(out_dir, "ligand_pharmacophores")
if not os.path.exists(p_out):
os.mkdir(p_out)
for n in [6, 5, 4, 3]:
lp = LigandPharmacophoreModel()
lp.detected_features = feats
lp.detected_features = lp.top_features(num=n)
for feat in lp.detected_features:
lp.add_feature(feat)
lp.intra_only = True
lp.write(os.path.join(p_out, f"{n}.cm"))
from hotspots.pharmacophore_extension import LigandPharmacophoreModel
from ccdc import io
csd = io.EntryReader('CSD')
crystal = csd.crystal('IBPRAC')
crystal.molecule.add_hydrogens()
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"acceptor_projected", "donor_projected", "ring_planar_projected"
]
ligand_pharmacophore.detect_from_ligand(crystal)
ligand_pharmacophore.pymol_visulisation()
def setUp(self):
self.csd = csd()
self.crystal = csd().crystal('AABHTZ')
self.crystal.molecule.add_hydrogens()
self.ligand_pharmacophore = LigandPharmacophoreModel()
class TestLigandPharmacophoreModel(unittest.TestCase):
def setUp(self):
self.csd = csd()
self.crystal = csd().crystal('AABHTZ')
self.crystal.molecule.add_hydrogens()
self.ligand_pharmacophore = LigandPharmacophoreModel()
def testSetters(self):
self.assertEqual(0, len(self.ligand_pharmacophore.features))
self.ligand_pharmacophore.feature_definitions = ["acceptor"]
self.assertEqual(1, len(self.ligand_pharmacophore.feature_definitions))
def testdetect_from_ligand(self):
wrkdir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand"
with PushDir(wrkdir):
self.ligand_pharmacophore.feature_definitions = ["acceptor"]
print(self.ligand_pharmacophore.feature_definitions["acceptor"].
point_generator_names)
self.ligand_pharmacophore.detect_from_ligand(ligand=self.crystal)
self.assertEqual(5,
len(self.ligand_pharmacophore.detected_features))
# test score setter
self.assertEqual(
0, self.ligand_pharmacophore.detected_features[0].score)
self.ligand_pharmacophore.detected_features[0].score = 5
self.assertEqual(
5, self.ligand_pharmacophore.detected_features[0].score)
# test write
for f in self.ligand_pharmacophore.detected_features:
self.ligand_pharmacophore.add_feature(f)
self.ligand_pharmacophore.write(
pharmacophore_path="pharmacophore.cm")
read_me = LigandPharmacophoreModel.from_file("pharmacophore.cm")
self.assertEqual(len(self.ligand_pharmacophore.features),
len(read_me.features))
print(read_me.features[0].spheres[0].centre)
# self.ligand_pharmacophore.pymol_visulisation()
def testto_pymol_str(self):
self.ligand_pharmacophore.feature_definitions = ["acceptor_projected"]
self.ligand_pharmacophore.detect_from_ligand(ligand=self.crystal)
f = PyMOLFile()
f.commands += self.ligand_pharmacophore.detected_features[
0].to_pymol_str()
f.write(
"testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand/feature_write.py"
)
def testdetect_from_pdb(self):
testpdb = "2vta"
testhetid = "LZ1"
testchainid = "A"
self.ligand_pharmacophore.feature_definitions = [
"donor_projected", "acceptor_projected"
]
self.ligand_pharmacophore.detect_from_pdb(pdb=testpdb,
hetid=testhetid,
chainid=testchainid)
self.assertEqual(2, len(self.ligand_pharmacophore.detected_features))
# self.ligand_pharmacophore.pymol_visulisation("testdata/pharmacophore_extension/LigandPharmacophoreModel/from_pdb")
def testdetect_from_ligand_ensemble(self):
wrk_dir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand_ensemble"
with PushDir(wrk_dir):
test_overlay = io.MoleculeReader("test_overlay.mol2")
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"ring_planar_projected"
]
ligand_pharmacophore.detect_from_ligand_ensemble(
ligands=test_overlay, cutoff=2)
# ligand_pharmacophore.pymol_visulisation(outdir="")
self.assertEqual(2, len(ligand_pharmacophore.detected_features))
def testdetect_from_ligand_ensemble_cdk2(self):
wrk_dir = "testdata/pharmacophore_extension/LigandPharmacophoreModel/from_ligand_ensemble_big_all"
with PushDir(wrk_dir):
test_overlay = io.MoleculeReader("cdk2_ligands.mol2")
ligand_pharmacophore = LigandPharmacophoreModel()
ligand_pharmacophore.feature_definitions = [
"ring_planar_projected", "donor_projected",
"acceptor_projected"
]
ligand_pharmacophore.detect_from_ligand_ensemble(
ligands=test_overlay, cutoff=2)
feature_count = 4
selected = ligand_pharmacophore.top_features(num=feature_count)
ligand_pharmacophore.detected_features = selected
self.assertEqual(feature_count, len(ligand_pharmacophore))