def get_hydrogen_bonding(self):
"""Gets hydrogen bonding character for all atoms.
Returns:
A dict mapping RDKit Atom indices to a HydrogenBonding object. Atom
indices not in the dict are neither acceptors nor donors.
Raises:
TypeError: if more than one atom index is associated with the same
acceptor or donor.
"""
self.check_indices()
factory = ChemicalFeatures.BuildFeatureFactoryFromString(_HBOND_FEATURE_DEF)
features = factory.GetFeaturesForMol(self.mol)
hb = collections.defaultdict(lambda: HydrogenBonding(False, False))
for feat in features:
family = feat.GetFamily().lower()
if family in ['acceptor', 'donor']:
if len(feat.GetAtomIds()) != 1:
raise TypeError('More than one atom index for %s.' % family)
idx = feat.GetAtomIds()[0]
# pylint:disable=protected-access
if family == 'acceptor':
hb[idx] = hb[idx]._replace(acceptor=True)
elif family == 'donor':
hb[idx] = hb[idx]._replace(donor=True)
# pylint:enable=protected-access
return hb
def setUp(self):
self.fdefBlock = \
"""DefineFeature HAcceptor1 [N,O;H0]
Family HBondAcceptor
Weights 1.0
EndFeature
DefineFeature HDonor1 [N,O;!H0]
Family HBondDonor
Weights 1.0
EndFeature
DefineFeature Aromatic1 c1ccccc1
Family Aromatic
Weights 1.0,1.0,1.0,1.0,1.0,1.0
EndFeature\n"""
self.featFactory = ChemicalFeatures.BuildFeatureFactoryFromString(
self.fdefBlock)
self.feats = [
ChemicalFeatures.FreeChemicalFeature(
'HBondAcceptor', 'HAcceptor1', Geometry.Point3D(0.0, 0.0,
0.0)),
ChemicalFeatures.FreeChemicalFeature(
'HBondDonor', 'HDonor1', Geometry.Point3D(2.65, 0.0, 0.0)),
ChemicalFeatures.FreeChemicalFeature(
'Aromatic', 'Aromatic1', Geometry.Point3D(5.12, 0.908, 0.0)),
]
self.pcophore = Pharmacophore.Pharmacophore(self.feats)
def setUp(self):
self.dataDir = os.path.join(RDConfig.RDCodeDir,
'Chem/Pharm3D/test_data')
self.fdefBlock = """
DefineFeature HAcceptor1 [N,O;H0]
Family HBondAcceptor
Weights 1.0
EndFeature
DefineFeature HDonor1 [N,O;!H0]
Family HBondDonor
Weights 1.0
EndFeature
DefineFeature Aromatic1 c1ccccc1
Family Aromatic
Weights 1.,1.,1.,1.,1.,1.
EndFeature\n"""
self.featFactory = ChemicalFeatures.BuildFeatureFactoryFromString(
self.fdefBlock)
self.feats = [
ChemicalFeatures.FreeChemicalFeature(
'HBondAcceptor', 'HAcceptor1', Geometry.Point3D(0.0, 0.0,
0.0)),
ChemicalFeatures.FreeChemicalFeature(
'HBondDonor', 'HDonor1', Geometry.Point3D(2.65, 0.0, 0.0)),
ChemicalFeatures.FreeChemicalFeature(
'Aromatic', 'Aromatic1', Geometry.Point3D(5.12, 0.908, 0.0)),
]
self.pcophore = Pharmacophore.Pharmacophore(self.feats)
self.pcophore.setLowerBound(0, 1, 2.0)
self.pcophore.setUpperBound(0, 1, 3.3)
self.pcophore.setLowerBound(0, 2, 5.0)
self.pcophore.setUpperBound(0, 2, 5.4)
self.pcophore.setLowerBound(1, 2, 2.6)
self.pcophore.setUpperBound(1, 2, 3.0)
def testAtomMatch(self):
fdefBlock = \
"""
DefineFeature HAcceptor1 [#7,#8]
Family HBondAcceptor
Weights 1.0
EndFeature
DefineFeature Arom1 a1aaaaa1
Family Aromatic
Weights 1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
"""
cfac = ChemicalFeatures.BuildFeatureFactoryFromString(fdefBlock)
self.failUnless(cfac.GetNumFeatureDefs() == 2)
mol = Chem.MolFromSmiles('n1ccccc1')
feats = cfac.GetFeaturesForMol(mol)
self.failUnless(len(feats)==2)
m = ChemicalFeatures.GetAtomMatch(feats)
self.failIf(m)
mol = Chem.MolFromSmiles('c1ccccc1N')
feats = cfac.GetFeaturesForMol(mol)
self.failUnless(len(feats)==2)
m = ChemicalFeatures.GetAtomMatch(feats)
self.failUnless(len(m)==2)
def testParseErrorHandling(self):
fdefBlock = \
"""DefineFeature HDonor1 [N,O;!HQ]
Family HBondDonor
Weights 1.0
EndFeature
"""
self.failUnlessRaises(ValueError,
lambda: ChemicalFeatures.BuildFeatureFactoryFromString(fdefBlock))
fdefBlock = \
"""DefineFeature HDonor1 [N,O;!H0]
Family HBondDonor
Weights 1.0
"""
self.failUnlessRaises(ValueError,
lambda: ChemicalFeatures.BuildFeatureFactoryFromString(fdefBlock))
self.failUnlessRaises(IOError, lambda: ChemicalFeatures.BuildFeatureFactory('noSuchFile.txt'))
def testStringParse(self):
fdefBlock = \
"""DefineFeature HDonor1 [N,O;!H0]
Family HBondDonor
Weights 1.0
EndFeature
DefineFeature HAcceptor1 [N,O;H0]
Family HBondAcceptor
Weights 1.0
EndFeature
"""
cfac = ChemicalFeatures.BuildFeatureFactoryFromString(fdefBlock)
self.failUnless(cfac.GetNumFeatureDefs() == 2)
def get_cats_factory(features='cats', names=False):
""" Get the feature combinations paired to all possible distances
:param features: {str} which pharmacophore features to consider; available: ["cats", "rdkit"]
:param names: {bool} whether to return an array describing the bits with names of features and distances
:return: RDKit signature factory to be used for 2D pharmacophore fingerprint calculation
"""
if features == 'cats':
fdef = fdef_cats
else:
fdef = fdef_rdkit
factory = ChemicalFeatures.BuildFeatureFactoryFromString(fdef)
sigfactory = SigFactory.SigFactory(factory, useCounts=True, minPointCount=2, maxPointCount=2)
sigfactory.SetBins([(0, 1), (1, 2), (2, 3), (3, 4), (4, 5), (5, 6), (6, 7), (7, 8), (8, 9), (9, 10)])
sigfactory.Init()
if names:
descs = [sigfactory.GetBitDescription(i) for i in range(sigfactory.GetSigSize())]
return sigfactory, descs
else:
return sigfactory
def testIssue231(self):
fdefs = """
DefineFeature HDonor1 [N,O;!H0]
Family HBondDonor
Weights 1.0
EndFeature
DefineFeature HAcceptor1 [N,O;H0]
Family HBondAcceptor
Weights 1.0
EndFeature
"""
cfac = ChemicalFeatures.BuildFeatureFactoryFromString(fdefs)
m = Chem.MolFromSmiles('O=CCCN')
rdDistGeom.EmbedMolecule(m)
feats = cfac.GetFeaturesForMol(m)
for feat in feats:
feat.GetPos()
m = None
for feat in feats:
feat.GetPos()
Weights 1.0,1.0,1.0,1.0,1.0
EndFeature
DefineFeature Arom6 a1aaaaa1
Family Aromatic
Weights 1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
DefineFeature Arom7 a1aaaaaa1
Family Aromatic
Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
DefineFeature Arom8 a1aaaaaaa1
Family Aromatic
Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
"""
featFactory = ChemicalFeatures.BuildFeatureFactoryFromString(fdefstr)
def CalculatePharm2D2pointFingerprint(mol, featFactory=featFactory):
"""
Calculate Pharm2D2point Fingerprints
"""
sigFactory_2point = SigFactory(featFactory,
minPointCount=2,
maxPointCount=2)
sigFactory_2point.SetBins([(0, 1), (1, 2), (2, 3), (3, 4), (4, 5), (5, 6),
(6, 7), (7, 8), (8, 9)])
sigFactory_2point.Init()
res = Generate.Gen2DFingerprint(mol, sigFactory_2point)
res_keys = tuple(res.GetOnBits())
def get_factory():
featFactory = ChemicalFeatures.BuildFeatureFactoryFromString(fdef)
factory = SigFactory(featFactory, minPointCount=2, maxPointCount=3, useCounts=True, trianglePruneBins=False)
factory.SetBins(defaultBins)
factory.Init()
return factory
def _init():
global labels, patts, factory
featFactory = ChemicalFeatures.BuildFeatureFactoryFromString(fdef)
factory = SigFactory(featFactory, minPointCount=2, maxPointCount=3)
factory.SetBins(defaultBins)
factory.Init()
def make_pharma_probes(target_id,
opt=None,
clash=-1.0,
rmsd=0.5,
shape_dist=0.2,
react_id=None):
"""Function to make a protein pharamcophore"""
target = Target.objects.get(pk=target_id)
tot_res = Residue.objects.filter(target_id=target_id)
if not opt:
# Do the proteins - but only a limited distance
# Make the limited description for these proteins
if react_id:
react_id.proc_stage = "MAKING PROTEIN PROBES"
react_id.stage_completion = 0
react_id.save()
factory = ChemicalFeatures.BuildFeatureFactoryFromString(prot_feats)
prots = Protein.objects.filter(
target_id=target,
pdb_info__isnull=False).exclude(code__contains=target.title)
tot_prots = len(prots)
# Loop through the mols
prot_old = -1
# for counter, p in enumerate(prots):
# # Trim the coords to X A from the ligand
# delta = 10.0
# prot_res = []
# if react_id:
# my_prg = int((float(counter) / float(tot_prots)) * 100)
# if my_prg != prot_old:
# react_id.stage_completion = my_prg
# prot_old = my_prg
# react_id.save()
# for mol in Molecule.objects.filter(prot_id=p):
# rdmol = Chem.MolFromMolBlock(str(mol.sdf_info))
## x_coords, y_coords, z_coords = get_all_coords(rdmol)
## x_max = max(x_coords)
## y_max = max(y_coords)
## z_max = max(z_coords)
## x_min = min(x_coords)
## y_min = min(y_coords)
## z_min = min(z_coords)
## near_res = tot_res.filter(prot_id=p).exclude(x_max__gte=x_max + delta, x_min__gte=x_min + delta).exclude(x_max__lte=x_max - delta, x_min__lte=x_min - delta)
## near_res = near_res.exclude(y_max__gte=y_max + delta, y_min__gte=y_min + delta).exclude(y_max__lte=y_max - delta, y_min__lte=y_min - delta)
## near_res = near_res.exclude(z_max__gte=z_max + delta, z_min__gte=z_min + delta).exclude(z_max__lte=z_max - delta, z_min__lte=z_min - delta)
## prot_res.extend(near_res)
# old = -1
# tot = len(prot_res)
# #for res_count, res in enumerate(prot_res):
for p in prots:
print p.code
## Mol2 required for hydrogens currently
if PlifProtein.objects.filter(prot_id=p):
rdmol = Chem.MolFromMol2Block(str(
PlifProtein.objects.filter(prot_id=p)[0].mol2_data),
removeHs=False)
else:
rdmol = Chem.MolFromPDBBlock(str(p.pdb_info))
# Add the Hs => but this is pretty ruddy dodgy
rdmol = AllChem.AddHs(rdmol, addCoords=True)
if rdmol is None:
print "ERROR WITH PROTEIN ", p.pk
continue
conf = rdmol.GetConformer()
feats = factory.GetFeaturesForMol(rdmol)
for i, feat in enumerate(feats):
# Assign the residue
info = rdmol.GetAtomWithIdx(
feat.GetAtomIds()[0]).GetPDBResidueInfo()
if info:
res_num = info.GetResidueNumber()
res_name = info.GetResidueName()
else:
res_num = i
res_name = "MOL2"
my_res = Residue.objects.get_or_create(target_id=target,
prot_id=p,
res_name=res_name,
res_num=res_num)[0]
new_fragment = init_probe(feat,
target,
mol_id=None,
res_id=my_res,
prot_id=p)
new_fragment.res_id = my_res
new_fragment.unique_id = "RES" + str(my_res.pk)
### Now we've set x_com
# Now validate this is in 1) a new place 2) a new feature 3) on a unique residue
new_fragment = assign_extents(new_fragment, conf, feat, rdmol)
if not new_fragment:
continue
# Now assign the atom_ids
new_fragment.atom_ids = str(feat.GetAtomIds())
try:
new_fragment.validate_unique()
except ValidationError:
new_fragment = PlifProbe.objects.get(
x_com=new_fragment.x_com,
y_com=new_fragment.y_com,
z_com=new_fragment.z_com,
unique_id=new_fragment.unique_id,
type=new_fragment.type)
new_fragment.atom_ids = str(feat.GetAtomIds())
new_fragment.save(update_fields=["atom_ids"])
continue
new_fragment.save()
sys.stdout.write("\rMaking Protein probes for protein complete")
sys.stdout.flush()
print "Made protein PLIFS"
# Different ph4s for these molecules
fdefName = os.path.join(
os.path.join(os.path.split(sys.argv[0])[0], 'data/media'),
'BaseFeatures.fdef')
factory = ChemicalFeatures.BuildFeatureFactory(fdefName)
# Get the molecules that relate to this
if not opt:
if react_id:
react_id.proc_stage = "MAKING MOLECULE PROBES"
react_id.stage_completion = 0
react_id.save()
mols = Molecule.objects.filter(prot_id__in=prots)
elif opt == "LLOOMMPPAA":
# Take the molecules from LLOOMMPPAA for testing
if react_id:
ll_confs = LLConf.objects.filter(target_id=target,
clash__gte=clash,
rmsd__gte=rmsd,
shape_dist__lte=shape_dist,
reactionprocess=react_id)
react_id.proc_stage = "MAKING LLOOMMPPAA PROBES"
react_id.stage_completion = 0
react_id.save()
else:
ll_confs = LLConf.objects.filter(target_id=target,
clash__gte=clash,
rmsd__gte=rmsd,
shape_dist__lte=shape_dist)
mols = [ll.mol_id for ll in ll_confs]
old = -1
tot = len(mols)
# List and counter to trigger the bulk create
new_counter = 0
new_fragments = []
done_list = []
mol_old = -1
print "Making probes for " + str(tot) + " molecules"
for counter, m in enumerate(mols):
if m.pk in done_list:
continue
done_list.append(m.pk)
sys.stdout.write("\rMaking molecule probes %d of %d complete..." %
(counter, tot))
sys.stdout.flush()
if react_id:
my_prg = int((float(counter) / float(tot)) * 100)
if my_prg != mol_old:
react_id.stage_completion = my_prg
mol_old = my_prg
react_id.save()
# Get the molecule
orig_mol = Chem.MolFromMolBlock(str(m.sdf_info))
# Add the Hydrogens
rdmol = AllChem.AddHs(orig_mol, addCoords=True)
# Get the conformer
conf = rdmol.GetConformer()
for feat in factory.GetFeaturesForMol(rdmol):
# Initialise this new object
new_fragment = init_probe(feat, target, mol_id=m)
new_fragment = assign_extents(new_fragment, conf, feat, rdmol,
"MOL")
if not new_fragment:
continue
# Now assign the atom_ids
new_fragment.atom_ids = str(feat.GetAtomIds())
try:
new_fragment.validate_unique()
new_fragment.save()
except ValidationError:
continue
new_fragments.append(new_fragment)
new_counter += 1
if new_counter == 5000:
print "COMMITING"
#PlifProbe.objects.bulk_create(new_fragments)
new_fragments = []
done_list = []
new_counter = 0
#PlifProbe.objects.bulk_create(new_fragments)
sys.stdout.write("\rMaking molecule probes %d%% complete..." % 100)
sys.stdout.flush()
print "Made molecule probes"
if not opt and react_id:
react_id.proc_stage = "MAKING LLOOMMPPAA PROBES"
react_id.stage_completion = -1
react_id.save()
elif react_id:
react_id.proc_stage = "FINDING INTERACTIONS"
react_id.stage_completion = -1
react_id.save()
