def _prepare_input_file(self, logger=None):
from rdkit import Chem
import rdkit.Chem.rdmolops as rd
self.parameters.input = "input.conf"
params = self.parameters
# Check input file
limit_atoms_ligand = 100
ch.check_limit_number_atoms(params.ligands, limit_atoms_ligand)
# Get core of the ligand
mol = Chem.MolFromPDBFile(params.core)
try:
ligand_core = rd.SplitMolByPDBResidues(mol)[params.residue]
except KeyError:
raise ce.MissResidueFlag("Missing residue flag to specify " +
"the ligand core residue name. " +
"i.e resname: 'LIG'")
# Get sdf full grown ligands
ligands_grown = Chem.SDMolSupplier(params.ligands, removeHs=False)
fragment_files = []
# For each full grown ligand create neutral fragment
with open(params.input, "w") as fout:
pass
for ligand in ligands_grown:
Chem.AssignAtomChiralTagsFromStructure(ligand)
try:
line, fragment = \
self._create_fragment_from_ligand(ligand,
ligand_core)
except Exception as e:
try:
line, fragment = \
self._create_fragment_from_ligand(ligand,
ligand_core,
substructure=False)
except Exception as e:
try:
# Try to fix symmetry
line, fragment = \
self._create_fragment_from_ligand(ligand,
ligand_core,
symmetry=True)
except Exception as e:
# Try with second substructure search
line, fragment = \
self._create_fragment_from_ligand(
ligand, ligand_core,
result=1, substructure=False)
logger.info(f"Ligand {fragment.file} preprocessed")
fragment_files.append(fragment.file)
with open(params.input, "a") as fout:
fout.write(line + "\n")
return fragment_files
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 _prepare_input_file(self):
from rdkit import Chem
import rdkit.Chem.rdmolops as rd
import rdkit.Chem.rdchem as rc
import rdkit.Chem.AllChem as rp
self.input = "input.conf"
#Check input file
limit_atoms_ligand = 100
ch.check_limit_number_atoms(self.ligands, limit_atoms_ligand)
#Get core of the ligand
mol = Chem.MolFromPDBFile(self.core)
try:
ligand_core = rd.SplitMolByPDBResidues(mol)[self.residue]
except KeyError:
raise ce.MissResidueFlag(
"Missing residue flag to specify the ligand core residue name. i.e resname: 'LIG'"
)
#Get sdf full grown ligands
ligands_grown = Chem.SDMolSupplier(self.ligands, removeHs=False)
#For each full grown ligand create neutral fragment
self.fragments = []
lines = []
for ligand in ligands_grown:
try:
line, fragment = self._create_fragment_from_ligand(
ligand, ligand_core)
except Exception as e:
try:
# Try to fix simmetry
line, fragment = self._create_fragment_from_ligand(
ligand, ligand_core, simmetry=True)
except Exception as e:
try:
# Try with second substructure search
line, fragment = self._create_fragment_from_ligand(
ligand, ligand_core, result=1, substructure=False)
except Exception as e:
#Skip the ligand
print("Ligand Skipped")
print(e)
continue
lines.append(line)
self.fragments.append(fragment)
print(f"Ligand {fragment.file} preprocessed")
with open(self.input, "w") as fout:
fout.write(("\n").join(lines))
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