def test_pdbqt_to_pdb(self):
current_dir = os.path.dirname(os.path.realpath(__file__))
protein_file = os.path.join(current_dir,
"../../dock/tests/1jld_protein.pdb")
xyz, mol = rdkit_util.load_molecule(
protein_file, calc_charges=False, add_hydrogens=False)
out_pdb = "/tmp/mol.pdb"
out_pdbqt = "/tmp/mol.pdbqt"
rdkit_util.write_molecule(mol, out_pdb)
rdkit_util.write_molecule(mol, out_pdbqt, is_protein=True)
pdb_block = rdkit_util.pdbqt_to_pdb(out_pdbqt)
pdb_mol = Chem.MolFromPDBBlock(pdb_block, sanitize=False, removeHs=False)
xyz, pdbqt_mol = rdkit_util.load_molecule(
out_pdbqt, add_hydrogens=False, calc_charges=False)
assert_equal(pdb_mol.GetNumAtoms(), pdbqt_mol.GetNumAtoms())
for atom_idx in range(pdb_mol.GetNumAtoms()):
atom1 = pdb_mol.GetAtoms()[atom_idx]
atom2 = pdbqt_mol.GetAtoms()[atom_idx]
assert_equal(atom1.GetAtomicNum(), atom2.GetAtomicNum())
os.remove(out_pdb)
os.remove(out_pdbqt)
def test_pdbqt_to_pdb(self):
current_dir = os.path.dirname(os.path.realpath(__file__))
protein_file = os.path.join(current_dir,
"../../dock/tests/1jld_protein.pdb")
xyz, mol = rdkit_util.load_molecule(protein_file,
calc_charges=False,
add_hydrogens=False)
out_pdb = "/tmp/mol.pdb"
out_pdbqt = "/tmp/mol.pdbqt"
rdkit_util.write_molecule(mol, out_pdb)
rdkit_util.write_molecule(mol, out_pdbqt, is_protein=True)
pdb_block = rdkit_util.pdbqt_to_pdb(out_pdbqt)
from rdkit import Chem
pdb_mol = Chem.MolFromPDBBlock(pdb_block,
sanitize=False,
removeHs=False)
xyz, pdbqt_mol = rdkit_util.load_molecule(out_pdbqt,
add_hydrogens=False,
calc_charges=False)
assert_equal(pdb_mol.GetNumAtoms(), pdbqt_mol.GetNumAtoms())
for atom_idx in range(pdb_mol.GetNumAtoms()):
atom1 = pdb_mol.GetAtoms()[atom_idx]
atom2 = pdbqt_mol.GetAtoms()[atom_idx]
assert_equal(atom1.GetAtomicNum(), atom2.GetAtomicNum())
os.remove(out_pdb)
os.remove(out_pdbqt)
def test_pdbqt_to_pdb(self):
"""Test that a PDBQT molecule can be converted back in to PDB."""
xyz, mol = rdkit_util.load_molecule(self.protein_file,
calc_charges=False,
add_hydrogens=False)
with tempfile.TemporaryDirectory() as tmp:
out_pdb = os.path.join(tmp, "mol.pdb")
out_pdbqt = os.path.join(tmp, "mol.pdbqt")
rdkit_util.write_molecule(mol, out_pdb, is_protein=True)
rdkit_util.write_molecule(mol, out_pdbqt, is_protein=True)
pdb_block = pdbqt_utils.pdbqt_to_pdb(out_pdbqt)
from rdkit import Chem
pdb_mol = Chem.MolFromPDBBlock(pdb_block,
sanitize=False,
removeHs=False)
xyz, pdbqt_mol = rdkit_util.load_molecule(out_pdbqt,
add_hydrogens=False,
calc_charges=False)
assert pdb_mol.GetNumAtoms() == pdbqt_mol.GetNumAtoms()
for atom_idx in range(pdb_mol.GetNumAtoms()):
atom1 = pdb_mol.GetAtoms()[atom_idx]
atom2 = pdbqt_mol.GetAtoms()[atom_idx]
assert atom1.GetAtomicNum() == atom2.GetAtomicNum()
def prepare_ligand(args):
mol_name, mol, save_dir = args[0], args[1], args[2]
filename = str(mol_name) + ".sdf"
filename = os.path.join(save_dir, filename)
rdkit_util.write_molecule(mol, filename)
prepared_filename = os.path.join(save_dir, "%s_prepared.pdb" % mol_name)
prepared_pdbqt = os.path.join(save_dir, "%s_prepared.pdbqt" % mol_name)
if os.path.exists(prepared_pdbqt):
return
hydrogenate_and_compute_partial_charges(filename,
"sdf",
hyd_output=prepared_filename,
pdbqt_output=prepared_pdbqt,
verbose=False,
protein=False)
def prepare_ligand(args):
mol_name, mol, save_dir = args[0], args[1], args[2]
filename = str(mol_name) + ".sdf"
filename = os.path.join(save_dir, filename)
rdkit_util.write_molecule(mol, filename)
prepared_filename = os.path.join(save_dir, "%s_prepared.pdb" % mol_name)
prepared_pdbqt = os.path.join(save_dir, "%s_prepared.pdbqt" % mol_name)
if os.path.exists(prepared_pdbqt):
return
hydrogenate_and_compute_partial_charges(
filename,
"sdf",
hyd_output=prepared_filename,
pdbqt_output=prepared_pdbqt,
verbose=False,
protein=False)
def hydrogenate_and_compute_partial_charges(input_file,
input_format,
hyd_output=None,
pdbqt_output=None,
protein=True,
verbose=True):
"""Outputs a hydrogenated pdb and a pdbqt with partial charges.
Takes an input file in specified format. Generates two outputs:
-) A pdb file that contains a hydrogenated (at pH 7.4) version of
original compound.
-) A pdbqt file that has computed Gasteiger partial charges. This pdbqt
file is build from the hydrogenated pdb.
TODO(rbharath): Can do a bit of refactoring between this function and
pdbqt_to_pdb.
Parameters
----------
input_file: String
Path to input file.
input_format: String
Name of input format.
"""
mol = rdkit_util.load_molecule(input_file,
add_hydrogens=True,
calc_charges=True)[1]
if verbose:
print("Create pdb with hydrogens added")
rdkit_util.write_molecule(mol, str(hyd_output), is_protein=protein)
if verbose:
print("Create a pdbqt file from the hydrogenated pdb above.")
rdkit_util.write_molecule(mol, str(pdbqt_output), is_protein=protein)
if protein:
print("Removing ROOT/ENDROOT/TORSDOF")
with open(pdbqt_output) as f:
pdbqt_lines = f.readlines()
filtered_lines = []
for line in pdbqt_lines:
filtered_lines.append(line)
with open(pdbqt_output, "w") as f:
f.writelines(filtered_lines)
def test_write_molecule(self):
current_dir = os.path.dirname(os.path.realpath(__file__))
ligand_file = os.path.join(current_dir, "../../dock/tests/1jld_ligand.sdf")
xyz, mol = rdkit_util.load_molecule(
ligand_file, calc_charges=False, add_hydrogens=False)
outfile = "/tmp/mol.sdf"
rdkit_util.write_molecule(mol, outfile)
xyz, mol2 = rdkit_util.load_molecule(
outfile, calc_charges=False, add_hydrogens=False)
assert_equal(mol.GetNumAtoms(), mol2.GetNumAtoms())
for atom_idx in range(mol.GetNumAtoms()):
atom1 = mol.GetAtoms()[atom_idx]
atom2 = mol.GetAtoms()[atom_idx]
assert_equal(atom1.GetAtomicNum(), atom2.GetAtomicNum())
os.remove(outfile)
def hydrogenate_and_compute_partial_charges(input_file,
input_format,
hyd_output=None,
pdbqt_output=None,
protein=True,
verbose=True):
"""Outputs a hydrogenated pdb and a pdbqt with partial charges.
Takes an input file in specified format. Generates two outputs:
-) A pdb file that contains a hydrogenated (at pH 7.4) version of
original compound.
-) A pdbqt file that has computed Gasteiger partial charges. This pdbqt
file is build from the hydrogenated pdb.
TODO(rbharath): Can do a bit of refactoring between this function and
pdbqt_to_pdb.
Parameters
----------
input_file: String
Path to input file.
input_format: String
Name of input format.
"""
mol = rdkit_util.load_molecule(
input_file, add_hydrogens=True, calc_charges=True)[1]
if verbose:
logging.info("Create pdb with hydrogens added")
rdkit_util.write_molecule(mol, str(hyd_output), is_protein=protein)
if verbose:
logging.info("Create a pdbqt file from the hydrogenated pdb above.")
rdkit_util.write_molecule(mol, str(pdbqt_output), is_protein=protein)
if protein:
logging.info("Removing ROOT/ENDROOT/TORSDOF")
with open(pdbqt_output) as f:
pdbqt_lines = f.readlines()
filtered_lines = []
for line in pdbqt_lines:
filtered_lines.append(line)
with open(pdbqt_output, "w") as f:
f.writelines(filtered_lines)
def test_write_molecule(self):
current_dir = os.path.dirname(os.path.realpath(__file__))
ligand_file = os.path.join(current_dir,
"../../dock/tests/1jld_ligand.sdf")
xyz, mol = rdkit_util.load_molecule(ligand_file,
calc_charges=False,
add_hydrogens=False)
with tempfile.TemporaryDirectory() as tmp:
outfile = os.path.join(tmp, "mol.sdf")
rdkit_util.write_molecule(mol, outfile)
xyz, mol2 = rdkit_util.load_molecule(outfile,
calc_charges=False,
add_hydrogens=False)
assert mol.GetNumAtoms() == mol2.GetNumAtoms()
for atom_idx in range(mol.GetNumAtoms()):
atom1 = mol.GetAtoms()[atom_idx]
atom2 = mol.GetAtoms()[atom_idx]
assert atom1.GetAtomicNum() == atom2.GetAtomicNum()
def test_write_molecule(self):
current_dir = os.path.dirname(os.path.realpath(__file__))
ligand_file = os.path.join(current_dir,
"../../dock/tests/1jld_ligand.sdf")
xyz, mol = rdkit_util.load_molecule(ligand_file,
calc_charges=False,
add_hydrogens=False)
outfile = "/tmp/mol.sdf"
rdkit_util.write_molecule(mol, outfile)
xyz, mol2 = rdkit_util.load_molecule(outfile,
calc_charges=False,
add_hydrogens=False)
assert_equal(mol.GetNumAtoms(), mol2.GetNumAtoms())
for atom_idx in range(mol.GetNumAtoms()):
atom1 = mol.GetAtoms()[atom_idx]
atom2 = mol.GetAtoms()[atom_idx]
assert_equal(atom1.GetAtomicNum(), atom2.GetAtomicNum())
os.remove(outfile)
def generate_poses(self,
molecular_complex,
centroid=None,
box_dims=None,
exhaustiveness=10,
num_modes=9,
num_pockets=None,
out_dir=None,
generate_scores=False):
"""Generates the docked complex and outputs files for docked complex.
TODO: How can this work on Windows? We need to install a .msi file and invoke it correctly from Python for this to work.
Parameters
----------
molecular_complexes: list
A representation of a molecular complex.
centroid: np.ndarray, optional
The centroid to dock against. Is computed if not specified.
box_dims: np.ndarray, optional
Of shape `(3,)` holding the size of the box to dock. If not
specified is set to size of molecular complex plus 5 angstroms.
exhaustiveness: int, optional (default 10)
Tells Autodock Vina how exhaustive it should be with pose
generation.
num_modes: int, optional (default 9)
Tells Autodock Vina how many binding modes it should generate at
each invocation.
num_pockets: int, optional (default None)
If specified, `self.pocket_finder` must be set. Will only
generate poses for the first `num_pockets` returned by
`self.pocket_finder`.
out_dir: str, optional
If specified, write generated poses to this directory.
generate_score: bool, optional (default False)
If `True`, the pose generator will return scores for complexes.
This is used typically when invoking external docking programs
that compute scores.
Returns
-------
Tuple of `(docked_poses, scores)`. `docked_poses` is a list of
docked molecular complexes. Each entry in this list contains a
`(protein_mol, ligand_mol)` pair of RDKit molecules. `scores` is a
list of binding free energies predicted by Vina.
Raises
------
`ValueError` if `num_pockets` is set but `self.pocket_finder is None`.
"""
if out_dir is None:
out_dir = tempfile.mkdtemp()
if num_pockets is not None and self.pocket_finder is None:
raise ValueError(
"If num_pockets is specified, pocket_finder must have been provided at construction time."
)
# Parse complex
if len(molecular_complex) > 2:
raise ValueError(
"Autodock Vina can only dock protein-ligand complexes and not more general molecular complexes."
)
(protein_file, ligand_file) = molecular_complex
# Prepare protein
protein_name = os.path.basename(protein_file).split(".")[0]
protein_hyd = os.path.join(out_dir, "%s_hyd.pdb" % protein_name)
protein_pdbqt = os.path.join(out_dir, "%s.pdbqt" % protein_name)
protein_mol = rdkit_util.load_molecule(
protein_file, calc_charges=True, add_hydrogens=True)
# Get protein centroid and range
if centroid is not None and box_dims is not None:
centroids = [centroid]
dimensions = [box_dims]
else:
if self.pocket_finder is None:
logger.info("Pockets not specified. Will use whole protein to dock")
rdkit_util.write_molecule(protein_mol[1], protein_hyd, is_protein=True)
rdkit_util.write_molecule(
protein_mol[1], protein_pdbqt, is_protein=True)
protein_centroid = geometry_utils.compute_centroid(protein_mol[0])
protein_range = mol_xyz_util.get_molecule_range(protein_mol[0])
box_dims = protein_range + 5.0
centroids, dimensions = [protein_centroid], [box_dims]
else:
logger.info("About to find putative binding pockets")
pockets = self.pocket_finder.find_pockets(protein_file)
logger.info("%d pockets found in total" % len(pockets))
logger.info("Computing centroid and size of proposed pockets.")
centroids, dimensions = [], []
for pocket in pockets:
protein_centroid = pocket.center()
(x_min, x_max), (y_min, y_max), (
z_min, z_max) = pocket.x_range, pocket.y_range, pocket.z_range
# TODO(rbharath: Does vina divide box dimensions by 2?
x_box = (x_max - x_min) / 2.
y_box = (y_max - y_min) / 2.
z_box = (z_max - z_min) / 2.
box_dims = (x_box, y_box, z_box)
centroids.append(protein_centroid)
dimensions.append(box_dims)
if num_pockets is not None:
logger.info("num_pockets = %d so selecting this many pockets for docking."
% num_pockets)
centroids = centroids[:num_pockets]
dimensions = dimensions[:num_pockets]
# Prepare protein
ligand_name = os.path.basename(ligand_file).split(".")[0]
ligand_pdbqt = os.path.join(out_dir, "%s.pdbqt" % ligand_name)
ligand_mol = rdkit_util.load_molecule(
ligand_file, calc_charges=True, add_hydrogens=True)
rdkit_util.write_molecule(ligand_mol[1], ligand_pdbqt)
docked_complexes = []
all_scores = []
for i, (protein_centroid, box_dims) in enumerate(
zip(centroids, dimensions)):
logger.info("Docking in pocket %d/%d" % (i + 1, len(centroids)))
logger.info("Docking with center: %s" % str(protein_centroid))
logger.info("Box dimensions: %s" % str(box_dims))
# Write Vina conf file
conf_file = os.path.join(out_dir, "conf.txt")
vina_utils.write_vina_conf(
protein_pdbqt,
ligand_pdbqt,
protein_centroid,
box_dims,
conf_file,
num_modes=num_modes,
exhaustiveness=exhaustiveness)
# Define locations of log and output files
log_file = os.path.join(out_dir, "%s_log.txt" % ligand_name)
out_pdbqt = os.path.join(out_dir, "%s_docked.pdbqt" % ligand_name)
logger.info("About to call Vina")
call(
"%s --config %s --log %s --out %s" % (self.vina_cmd, conf_file,
log_file, out_pdbqt),
shell=True)
ligands, scores = vina_utils.load_docked_ligands(out_pdbqt)
docked_complexes += [(protein_mol[1], ligand) for ligand in ligands]
all_scores += scores
if generate_scores:
return docked_complexes, all_scores
else:
return docked_complexes