def getMoleculeFromAtom(atom: Chem.BasicAtom, protein: Chem.BasicMolecule) -> (Chem.BasicMolecule, list):
"""
Given an atom and a protein structure, find the ligand the atom corresponds to.
Traverses the molecule by its bonds until no longer any atoms are attached. All atoms and bonds are assigned to a
new molecule, which is being returned.
:param atom:
:param protein:
:return: The found ligand as well as the atom indices of the ligand in the parent molecule.
"""
ligand = Chem.Fragment()
neighbors = set() # atoms not being added already
neighborsAdded = set() # keep track of added atoms to not process twice
atomsToRemove = []
neighbors.add(atom)
while len(neighbors) > 0:
n = neighbors.pop()
neighborsAdded.add(n)
ligand.addAtom(n)
atomsToRemove.append(protein.getAtomIndex(n))
# get all the neighbor atoms
for i, b in enumerate(n.bonds):
for a in b.atoms:
if a != n:
if a not in neighbors and a not in neighborsAdded: # new atom
neighbors.add(a)
ligand.addBond(b) # ignored if already exists
Chem.perceiveComponents(ligand, True)
mol = Chem.BasicMolecule()
mol.assign(ligand)
return mol, atomsToRemove
def _CDPLextractProteinFragments(pdb_mol, lig_three_letter_code, radius=6.0):
lig = Chem.Fragment()
_CDPLcalcProteinProperties(pdb_mol)
# extract ligand
for atom in pdb_mol.atoms:
if Biomol.getResidueCode(atom) == lig_three_letter_code:
Biomol.extractResidueSubstructure(atom, pdb_mol, lig, False)
if lig.numAtoms == 0:
log.error("The defined three letter code is not existing:",
lig_three_letter_code)
# extract environment
env = Chem.Fragment()
Biomol.extractEnvironmentResidues(lig, pdb_mol, env, float(radius))
return env, lig
def getSurfaceAtoms(mol):
surfaceATomExtractor = Chem.SurfaceAtomExtractor()
f = Chem.Fragment()
surfaceATomExtractor.extract(mol, mol, f)
surfaceAtoms = Chem.BasicMolecule()
surfaceAtoms.assign(f)
return surfaceAtoms
def getPh4InteractionDictionary(cdf_path, ligand_code):
ph4_interaction_dictionary = {}
cdf_mol = loadCDFMolecule(cdf_path)
num_confs = Chem.getNumConformations(cdf_mol)
ligand = Chem.Fragment()
for atom in cdf_mol.atoms:
if Biomol.getResidueCode(atom) == ligand_code:
Biomol.extractResidueSubstructure(atom, cdf_mol, ligand, False)
break
if ligand.numAtoms == 0:
print('> Could not find ligand {}'.format(ligand_code))
return 0
Chem.perceiveSSSR(ligand, True)
lig_env = Chem.Fragment()
lig_pharm = Pharm.BasicPharmacophore()
env_pharm = Pharm.BasicPharmacophore()
pharm_gen = Pharm.DefaultPharmacophoreGenerator(True)
analyzer = Pharm.DefaultInteractionAnalyzer()
interactions = Pharm.FeatureMapping()
for y in range(num_confs):
lig_pharm.clear()
env_pharm.clear()
interactions.clear()
lig_env.clear()
coords_func = Chem.AtomConformer3DCoordinatesFunctor(y)
pharm_gen.setAtom3DCoordinatesFunction(coords_func)
Biomol.extractEnvironmentResidues(ligand, cdf_mol, lig_env,
coords_func, 7)
Chem.perceiveSSSR(lig_env, True)
pharm_gen.generate(ligand, lig_pharm)
pharm_gen.generate(lig_env, env_pharm)
analyzer.analyze(lig_pharm, env_pharm, interactions)
ph4_interaction_dictionary[y] = getPh4Interactions(
lig_pharm, interactions)
return ph4_interaction_dictionary
def generate_ph(pdb, key):
ifs = Base.FileIOStream(pdb, 'r')
tlc = self.ligand_3_letter_code
pdb_reader = Biomol.PDBMoleculeReader(ifs)
pdb_mol = Chem.BasicMolecule()
print '- Reading input: ', pdb, ' ...'
if not pdb_reader.read(pdb_mol):
print '!! Could not read input molecule'
return
print '- Processing macromolecule', pdb, ' ...'
i = 0
while i < pdb_mol.getNumBonds():
bond = pdb_mol.getBond(i)
if Chem.isMetal(bond.atoms[0]) or Chem.isMetal(bond.atoms[1]):
pdb_mol.removeBond(i)
else:
i += 1
Chem.calcImplicitHydrogenCounts(pdb_mol, True)
Chem.perceiveHybridizationStates(pdb_mol, True)
Chem.makeHydrogenComplete(pdb_mol)
Chem.setAtomSymbolsFromTypes(pdb_mol, False)
Chem.calcImplicitHydrogenCounts(pdb_mol, True)
Biomol.setHydrogenResidueSequenceInfo(pdb_mol, False)
Chem.setRingFlags(pdb_mol, True)
Chem.setAromaticityFlags(pdb_mol, True)
Chem.generateHydrogen3DCoordinates(pdb_mol, True)
ligand = Chem.Fragment()
print '- Extracting ligand ', tlc, ' ...'
for atom in pdb_mol.atoms:
if Biomol.getResidueCode(atom) == tlc:
Biomol.extractResidueSubstructure(atom, pdb_mol, ligand,
False)
break
if ligand.numAtoms == 0:
print '!! Could not find ligand', tlc, 'in input file'
return
Chem.perceiveSSSR(ligand, True)
lig_env = Chem.Fragment()
Biomol.extractEnvironmentResidues(ligand, pdb_mol, lig_env, 7.0)
Chem.perceiveSSSR(lig_env, True)
print '- Constructing pharmacophore ...'
lig_pharm = Pharm.BasicPharmacophore()
env_pharm = Pharm.BasicPharmacophore()
pharm_gen = Pharm.DefaultPharmacophoreGenerator(False)
pharm_gen.generate(ligand, lig_pharm)
pharm_gen.generate(lig_env, env_pharm)
analyzer = Pharm.DefaultInteractionAnalyzer()
interactions = Pharm.FeatureMapping()
analyzer.analyze(lig_pharm, env_pharm, interactions)
#------------------------- XVOLS
int_env_ftrs = Pharm.FeatureSet()
Pharm.getFeatures(int_env_ftrs, interactions, False)
int_core_ftrs = Pharm.FeatureSet()
Pharm.getFeatures(int_core_ftrs, interactions, True)
int_pharm = Pharm.BasicPharmacophore(int_core_ftrs)
for ftr in int_env_ftrs:
if Pharm.getType(
ftr
) == Pharm.FeatureType.H_BOND_DONOR or Pharm.getType(
ftr) == Pharm.FeatureType.H_BOND_ACCEPTOR:
Pharm.setTolerance(ftr, 1.0)
else:
Pharm.setTolerance(ftr, 1.5)
Pharm.createExclusionVolumes(int_pharm, int_env_ftrs, 0.0, 0.1,
False)
int_env_ftr_atoms = Chem.Fragment()
Pharm.getFeatureAtoms(int_env_ftrs, int_env_ftr_atoms)
int_residue_atoms = Chem.Fragment()
Biomol.extractResidueSubstructures(int_env_ftr_atoms, lig_env,
int_residue_atoms, True)
Chem.makeHydrogenDeplete(int_residue_atoms)
def isAlphaAtom(atom):
return Biomol.getResidueAtomName(atom) == 'CA'
Chem.removeAtomsIfNot(int_residue_atoms, isAlphaAtom)
Pharm.createExclusionVolumes(int_pharm, int_residue_atoms,
Chem.Atom3DCoordinatesFunctor(), 1.0,
2.0, False)
features_in_ph = []
for int_ftr in int_pharm:
if Pharm.hasSubstructure(int_ftr) == False:
continue
elif ftype_names[Pharm.getType(int_ftr)] == 'XV':
continue
feature_id = generate_key(int_ftr)
features_in_ph.append(str(feature_id))
self.unique_feature_vector.add(str(feature_id))
int_pharm.fv = features_in_ph
int_pharm.path_to_pdb = pdb
return int_pharm
def generate_ph(pdb, args, df_constructor, ts):
ifs = Base.FileIOStream(pdb, 'r')
tlc = args.ligand_three_letter_code
pdb_reader = Biomol.PDBMoleculeReader(ifs)
pdb_mol = Chem.BasicMolecule()
print '- Reading input: ', pdb, ' ...'
if not pdb_reader.read(pdb_mol):
print '!! Could not read input molecule'
return
print '- Processing macromolecule', pdb, ' ...'
i = 0
while i < pdb_mol.getNumBonds():
bond = pdb_mol.getBond(i)
if Chem.isMetal(bond.atoms[0]) or Chem.isMetal(bond.atoms[1]):
pdb_mol.removeBond(i)
else:
i += 1
for a in pdb_mol.atoms:
Chem.setImplicitHydrogenCount(a, 0)
Chem.calcImplicitHydrogenCounts(pdb_mol, True)
Chem.perceiveHybridizationStates(pdb_mol, True)
Chem.makeHydrogenComplete(pdb_mol)
Chem.setAtomSymbolsFromTypes(pdb_mol, False)
Chem.calcImplicitHydrogenCounts(pdb_mol, True)
Biomol.setHydrogenResidueSequenceInfo(pdb_mol, False)
Chem.setRingFlags(pdb_mol, True)
Chem.setAromaticityFlags(pdb_mol, True)
Chem.generateHydrogen3DCoordinates(pdb_mol, True)
Chem.calcFormalCharges(pdb_mol, True)
ligand = Chem.Fragment()
print '- Extracting ligand ', tlc, ' ...'
for atom in pdb_mol.atoms:
if Biomol.getResidueCode(atom) == tlc:
Biomol.extractResidueSubstructure(atom, pdb_mol, ligand, False)
break
if ligand.numAtoms == 0:
print '!! Could not find ligand', tlc, 'in input file'
return
Chem.perceiveSSSR(ligand, True)
lig_env = Chem.Fragment()
Biomol.extractEnvironmentResidues(ligand, pdb_mol, lig_env, 7.0)
Chem.perceiveSSSR(lig_env, True)
print '- Constructing pharmacophore ...'
lig_pharm = Pharm.BasicPharmacophore()
env_pharm = Pharm.BasicPharmacophore()
pharm_gen = Pharm.DefaultPharmacophoreGenerator(True)
pharm_gen.generate(ligand, lig_pharm)
pharm_gen.generate(lig_env, env_pharm)
#Pharm.FilePMLFeatureContainerWriter('./test/lig_ph_' + str(ts) + '.pml').write(lig_pharm)
analyzer = Pharm.DefaultInteractionAnalyzer()
interactions = Pharm.FeatureMapping()
analyzer.analyze(lig_pharm, env_pharm, interactions)
df_constructor, interaction_at_ts = outputInteractions(
lig_pharm, env_pharm, interactions, df_constructor)
#Chem.FileSDFMolecularGraphWriter('./test/ligand_' + str(ts) + '.sdf').write(ligand)
return df_constructor, interaction_at_ts
