def _retrieve_fragment(fragment, old_atoms, atom_core, hydrogen_core, atom_fragment, mapping):
from rdkit import Chem
# Get new added hydrogen
try:
added_hydrogen_idx = [atom.GetIdx() for atom in fragment.GetAtoms() if atom.GetIdx() not in old_atoms][0]
no_hydrogens = False
# Get fragment atom attached to newly added hydrogen
atom_fragment_idx = fragment.GetAtomWithIdx(added_hydrogen_idx).GetNeighbors()[0].GetIdx()
except IndexError:
logger.info("Hydrogen detection failed won't have into account steriochemistry")
added_hydrogen_idx = 0
no_hydrogens = True
atom_fragment_idx = mapping[atom_fragment]
print("Final atom fragment", atom_fragment_idx)
# Save fragment
string = random_string(8)
fragment_filename = fragment.GetProp("_Name").replace(" ", "_") + string + ".pdb"
Chem.MolToPDBFile(fragment, fragment_filename)
fragment = Chem.MolFromPDBFile(fragment_filename, removeHs=False)
added_hydrogen = at.Atom(fragment, added_hydrogen_idx)
atom_fragment_attach_to_hydrogen = at.Atom(fragment, atom_fragment_idx)
# Build fragment object
fragment = fr.Fragment(fragment_filename, atom_fragment_attach_to_hydrogen,
added_hydrogen, atom_core, hydrogen_core, no_hydrogens)
return fragment
def _retrieve_fragment(fragment, old_atoms, atom_core, hydrogen_core):
from rdkit import Chem
import rdkit.Chem.rdmolops as rd
import rdkit.Chem.rdchem as rc
# Get new added hydrogen
try:
added_hydrogen_idx = [
atom.GetIdx() for atom in fragment.GetAtoms()
if atom.GetIdx() not in old_atoms
][0]
no_hydrogens = False
except IndexError:
print(
"Hydrogen detection failed won't have into account steriochemistry"
)
added_hydrogen_idx = 0
no_hydrogens = True
# Get fragment atom attached to newly added hydrogen
atom_fragment_idx = fragment.GetAtomWithIdx(
added_hydrogen_idx).GetNeighbors()[0].GetIdx()
# Save fragment
fragment_filename = fragment.GetProp("_Name") + ".pdb"
Chem.MolToPDBFile(fragment, fragment_filename)
fragment = Chem.MolFromPDBFile(fragment_filename, removeHs=False)
added_hydrogen = at.Atom(fragment, added_hydrogen_idx)
atom_fragment_attach_to_hydrogen = at.Atom(fragment, atom_fragment_idx)
# Build fragment object
fragment = fr.Fragment(fragment_filename, atom_fragment_attach_to_hydrogen,
added_hydrogen, atom_core, hydrogen_core,
no_hydrogens)
return fragment
def _build_fragment_from_complex(complex,
residue,
ligand,
ligand_core,
result=0,
substructure=True,
simmetry=False):
from rdkit import Chem
import rdkit.Chem.rdmolops as rd
import rdkit.Chem.rdchem as rc
import rdkit.Chem.AllChem as rp
#Retrieve atom core linking fragment
try:
atom_core_idx, atoms_core, _ = _search_core_fragment_linker(
ligand, ligand_core, result, simmetry)
except TypeError:
raise ce.SameMolecule(
"Core and ligand are the exact same molecule. Check your inputs")
atom_core = at.Atom(ligand_core, atom_core_idx)
mol = Chem.MolFromPDBFile(complex, removeHs=False)
#Retrieve hydrogen core attach to linking atom
original = rd.SplitMolByPDBResidues(mol)[residue]
hydrogen_core_idx = [
atom.GetIdx()
for atom in original.GetAtomWithIdx(atom_core_idx).GetNeighbors()
if atom.GetAtomicNum() == 1
][0]
hydrogen_core = at.Atom(original, hydrogen_core_idx)
# Delete core for full ligand with substructure
# and if it fails manually
#Chem.MolToPDBFile(ligand, "int0.pdb")
if substructure:
fragment = rd.DeleteSubstructs(ligand, ligand_core)
new_mol = rc.EditableMol(fragment)
for atom in reversed(fragment.GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0: new_mol.RemoveAtom(atom.GetIdx())
else:
new_mol = rc.EditableMol(ligand)
for atom in atoms_core:
new_mol.RemoveAtom(atom)
#Chem.MolToPDBFile(new_mol.GetMol(), "int1.pdb")
for atom in reversed(new_mol.GetMol().GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0: new_mol.RemoveAtom(atom.GetIdx())
#Add missing hydrogen to full ligand and create pdb differently
#depending on the previous step
fragment = new_mol.GetMol()
#Chem.MolToPDBFile(fragment, "int2.pdb")
old_atoms = [atom.GetIdx() for atom in fragment.GetAtoms()]
if substructure:
fragment = Chem.AddHs(fragment, False, True)
else:
#res = rp.EmbedMolecule(fragment)
fragment = Chem.AddHs(fragment, False, True)
return fragment, old_atoms, hydrogen_core, atom_core
def _build_fragment_from_complex(complex, residue, ligand, ligand_core, result=0, substructure=True, simmetry=False):
from rdkit import Chem
import rdkit.Chem.rdmolops as rd
import rdkit.Chem.rdchem as rc
# Retrieve atom core linking fragment
try:
atom_core_idx, atoms_core, atom_fragment = _search_core_fragment_linker(ligand, ligand_core, result, simmetry)
print("ATOM OF FRAGMENT ATTACHED TO CORE:", atom_fragment)
print("ATOM OF CORE ATTACHED TO FRAGMENT:", atom_core_idx)
except TypeError:
raise ce.SameMolecule("Core and ligand are the exact same molecule. Check your inputs.")
atom_core = at.Atom(ligand_core, atom_core_idx)
mol = Chem.MolFromPDBFile(complex, removeHs=False)
# Retrieve hydrogen core attach to linking atom
original = rd.SplitMolByPDBResidues(mol)[residue]
hydrogen_core_idx = \
[atom.GetIdx() for atom in original.GetAtomWithIdx(atom_core_idx).GetNeighbors() if atom.GetAtomicNum() == 1][0]
hydrogen_core = at.Atom(original, hydrogen_core_idx)
# Delete core for full ligand with substructure and if it fails manually
if substructure:
fragment = rd.DeleteSubstructs(ligand, ligand_core)
new_mol = rc.EditableMol(fragment)
for atom in reversed(fragment.GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0 and atom.GetAtomicNum() == 1:
new_mol.RemoveAtom(atom.GetIdx())
else:
new_mol = rc.EditableMol(ligand)
for atom in reversed(atoms_core):
new_mol.RemoveAtom(atom)
for atom in reversed(new_mol.GetMol().GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0 and atom.GetAtomicNum() == 1:
new_mol.RemoveAtom(atom.GetIdx())
print("FRAGMENT ATOMS", [atom.GetIdx() for atom in new_mol.GetMol().GetAtoms()])
# Add missing hydrogen to full ligand and create pdb differently depending on the previous step
fragment = new_mol.GetMol()
old_atoms = [atom.GetIdx() for atom in fragment.GetAtoms() if atom.GetAtomicNum() != 1]
new_atoms = [atom.GetIdx() for atom in ligand.GetAtoms() if
atom.GetIdx() not in atoms_core and atom.GetAtomicNum() != 1]
print("old_atoms", old_atoms, "new_atoms", new_atoms)
mapping = {new_atom: old_atom for new_atom, old_atom in zip(new_atoms, old_atoms)}
atom_fragment_mapped = mapping[atom_fragment]
fragment = Chem.AddHs(fragment, False, True)
correct = _check_fragment(fragment, ligand, mapping, atom_fragment, atom_fragment_mapped, ligand_core)
Chem.MolToPDBFile(fragment, "int0.pdb")
assert len(old_atoms) == len(new_atoms)
return fragment, old_atoms, hydrogen_core, atom_core, atom_fragment, mapping, correct
def _build_fragment_from_complex(complex,
residue,
ligand,
ligand_core,
result=0,
substructure=True,
symmetry=False,
frag_core_atom=None):
"""
Parameters
----------
complex : str
Path of PDB file with protein-ligand complex.
residue : str
Residue name.
ligand : RDKit molecule object
Ligand to grow during the simulation.
ligand_core : RDKit molecule object
Common structure of each grown ligand.
result : int
Index to extract core atoms from the substructure search.
substructure : bool
Delete core for full ligand with substructure.
symmetry : bool
Check the symmetry of the ligand.
Returns
-------
fragment : RDKit molecule object
Grown ligand with deleted core atoms.
old_atoms : list
Idx for each atom of grown ligand without core.
hydrogen_core : pele_platform.Frag.atoms.Atom
Hydrogen core attached to linking atom.
atom_core : pele_platform.Frag.atoms.Atom
Atom object of the hydrogen core atom attached to linking atom.
atom_fragment : int
Atom of the fragment attached to the core.
mapping : dict
Mapping of Idx for old atoms and full fragment atoms.
correct : bool
Checks if the fragment is correct (fragment size, chirality, missing hydrogens)
Raises
------
TypeError
If the core and ligand are the same molecule.
"""
# Retrieve atom core linking fragment
try:
atom_core_idx, atoms_core, atom_fragment = _search_core_fragment_linker(
ligand, ligand_core, result, symmetry, frag_core_atom)
print("ATOM OF FRAGMENT ATTACHED TO CORE:", atom_fragment)
print("ATOM OF CORE ATTACHED TO FRAGMENT:", atom_core_idx)
except TypeError:
raise ce.SameMolecule(
"Core and ligand are the exact same molecule. Check your inputs.")
atom_core = at.Atom(ligand_core, atom_core_idx)
mol = Chem.MolFromPDBFile(complex, removeHs=False)
# Retrieve hydrogen core attach to linking atom
original = rd.SplitMolByPDBResidues(mol)[residue]
hydrogen_core_idx = \
[atom.GetIdx() for atom in original.GetAtomWithIdx(atom_core_idx).GetNeighbors() if atom.GetAtomicNum() == 1][0]
hydrogen_core = at.Atom(original, hydrogen_core_idx)
# Delete core for full ligand with substructure and if it fails manually
if substructure:
fragment = rd.DeleteSubstructs(ligand, ligand_core)
new_mol = rc.EditableMol(fragment)
for atom in reversed(fragment.GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0 and atom.GetAtomicNum() == 1:
new_mol.RemoveAtom(atom.GetIdx())
else:
new_mol = rc.EditableMol(ligand)
for atom in reversed(atoms_core):
new_mol.RemoveAtom(atom)
for atom in reversed(new_mol.GetMol().GetAtoms()):
neighbours = atom.GetNeighbors()
if len(neighbours) == 0 and atom.GetAtomicNum() == 1:
new_mol.RemoveAtom(atom.GetIdx())
print("FRAGMENT ATOMS",
[atom.GetIdx() for atom in new_mol.GetMol().GetAtoms()])
# Add missing hydrogen to full ligand and create pdb differently depending on the previous step
fragment = new_mol.GetMol()
old_atoms = [
atom.GetIdx() for atom in fragment.GetAtoms()
if atom.GetAtomicNum() != 1
]
new_atoms = [
atom.GetIdx() for atom in ligand.GetAtoms()
if atom.GetIdx() not in atoms_core and atom.GetAtomicNum() != 1
]
print("old_atoms", old_atoms, "new_atoms", new_atoms)
mapping = {
new_atom: old_atom
for new_atom, old_atom in zip(new_atoms, old_atoms)
}
atom_fragment_mapped = mapping[atom_fragment]
# Retrieve all atom idxs before adding hydrogen to fragment_atom
fragment_atoms_wo_hydrogen = [
atom.GetIdx() for atom in fragment.GetAtoms()
]
fragment = Chem.AddHs(fragment, False, True)
correct = _check_fragment(fragment, ligand, mapping, atom_fragment,
atom_fragment_mapped, ligand_core)
Chem.MolToPDBFile(fragment, "int0.pdb")
assert len(old_atoms) == len(new_atoms)
return fragment, old_atoms, hydrogen_core, atom_core, atom_fragment, mapping, correct, fragment_atoms_wo_hydrogen
def _retrieve_fragment(fragment, old_atoms, atom_core, hydrogen_core,
atom_fragment, mapping, fragment_atoms_wo_hydrogen):
"""
Parameters
----------
old_atoms : list
Idx for each atom of grown ligand without core.
atom_core : pele_platform.Frag.atoms.Atom
Atom object of the hydrogen core atom attached to linking atom.
hydrogen_core : pele_platform.Frag.atoms.Atom
Hydrogen core attached to linking atom.
atom_fragment : int
Atom of the fragment attached to the core.
mapping : dict
Mapping of Idx for old atoms and full fragment atoms.
Returns
-------
fragment : pele_platform.Frag.fragments.Fragment
Fragment grown to the ligand during the simulation.
Raises
------
IndexError
If the hydrogen detection failed.
"""
from rdkit import Chem
# Get new added hydrogen
try:
# Identify idx from added hydrogen
added_hydrogen_idx = [
atom.GetIdx() for atom in fragment.GetAtoms()
if atom.GetIdx() not in fragment_atoms_wo_hydrogen
][0]
no_hydrogens = False
# Get fragment atom attached to newly added hydrogen
atom_fragment_idx = fragment.GetAtomWithIdx(
added_hydrogen_idx).GetNeighbors()[0].GetIdx()
except IndexError:
print(
"Hydrogen detection failed won't have into account stereochemistry"
)
added_hydrogen_idx = 0
no_hydrogens = True
atom_fragment_idx = mapping[atom_fragment]
print("Final atom fragment", atom_fragment_idx)
# Save fragment
string = random_string(8)
fragment_filename = fragment.GetProp("_Name").replace(
" ", "_") + string + ".pdb"
Chem.MolToPDBFile(fragment, fragment_filename)
fragment = Chem.MolFromPDBFile(fragment_filename, removeHs=False)
added_hydrogen = at.Atom(fragment, added_hydrogen_idx)
atom_fragment_attach_to_hydrogen = at.Atom(fragment, atom_fragment_idx)
# Build fragment object
fragment = fr.Fragment(fragment_filename, atom_fragment_attach_to_hydrogen,
added_hydrogen, atom_core, hydrogen_core,
no_hydrogens)
return fragment