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from openbabel import pybel
from meeko import MoleculePreparation
from meeko import obutils
from vina import Vina
import subprocess
import rdkit.Chem as Chem
from rdkit.Chem import AllChem
import tempfile
import AutoDockTools
import os
import contextlib
from utils.reconstruct import reconstruct_from_generated
from utils.evaluation.docking_qvina import get_random_id, BaseDockingTask
def supress_stdout(func):
def wrapper(*a, **ka):
with open(os.devnull, 'w') as devnull:
with contextlib.redirect_stdout(devnull):
return func(*a, **ka)
return wrapper
class PrepLig(object):
def __init__(self, input_mol, mol_format):
if mol_format == 'smi':
self.ob_mol = pybel.readstring('smi', input_mol)
elif mol_format == 'sdf':
self.ob_mol = next(pybel.readfile(mol_format, input_mol))
else:
raise ValueError(f'mol_format {mol_format} not supported')
def addH(self, polaronly=False, correctforph=True, PH=7):
self.ob_mol.OBMol.AddHydrogens(polaronly, correctforph, PH)
obutils.writeMolecule(self.ob_mol.OBMol, 'tmp_h.sdf')
def gen_conf(self):
sdf_block = self.ob_mol.write('sdf')
rdkit_mol = Chem.MolFromMolBlock(sdf_block, removeHs=False)
AllChem.EmbedMolecule(rdkit_mol, Chem.rdDistGeom.ETKDGv3())
self.ob_mol = pybel.readstring('sdf', Chem.MolToMolBlock(rdkit_mol))
obutils.writeMolecule(self.ob_mol.OBMol, 'conf_h.sdf')
@supress_stdout
def get_pdbqt(self, lig_pdbqt=None):
preparator = MoleculePreparation()
preparator.prepare(self.ob_mol.OBMol)
if lig_pdbqt is not None:
preparator.write_pdbqt_file(lig_pdbqt)
return
else:
return preparator.write_pdbqt_string()
class PrepProt(object):
def __init__(self, pdb_file):
self.prot = pdb_file
def del_water(self, dry_pdb_file): # optional
with open(self.prot) as f:
lines = [l for l in f.readlines() if l.startswith('ATOM') or l.startswith('HETATM')]
dry_lines = [l for l in lines if not 'HOH' in l]
with open(dry_pdb_file, 'w') as f:
f.write(''.join(dry_lines))
self.prot = dry_pdb_file
def addH(self, prot_pqr): # call pdb2pqr
self.prot_pqr = prot_pqr
subprocess.Popen(['pdb2pqr30','--ff=AMBER',self.prot, self.prot_pqr],
stderr=subprocess.DEVNULL, stdout=subprocess.DEVNULL).communicate()
def get_pdbqt(self, prot_pdbqt):
prepare_receptor = os.path.join(AutoDockTools.__path__[0], 'Utilities24/prepare_receptor4.py')
subprocess.Popen(['python3', prepare_receptor, '-r', self.prot_pqr, '-o', prot_pdbqt],
stderr=subprocess.DEVNULL, stdout=subprocess.DEVNULL).communicate()
class VinaDock(object):
def __init__(self, lig_pdbqt, prot_pdbqt):
self.lig_pdbqt = lig_pdbqt
self.prot_pdbqt = prot_pdbqt
def _max_min_pdb(self, pdb, buffer):
with open(pdb, 'r') as f:
lines = [l for l in f.readlines() if l.startswith('ATOM') or l.startswith('HEATATM')]
xs = [float(l[31:39]) for l in lines]
ys = [float(l[39:47]) for l in lines]
zs = [float(l[47:55]) for l in lines]
print(max(xs), min(xs))
print(max(ys), min(ys))
print(max(zs), min(zs))
pocket_center = [(max(xs) + min(xs))/2, (max(ys) + min(ys))/2, (max(zs) + min(zs))/2]
box_size = [(max(xs) - min(xs)) + buffer, (max(ys) - min(ys)) + buffer, (max(zs) - min(zs)) + buffer]
return pocket_center, box_size
def get_box(self, ref=None, buffer=0):
'''
ref: reference pdb to define pocket.
buffer: buffer size to add
if ref is not None:
get the max and min on x, y, z axis in ref pdb and add buffer to each dimension
else:
use the entire protein to define pocket
'''
if ref is None:
ref = self.prot_pdbqt
self.pocket_center, self.box_size = self._max_min_pdb(ref, buffer)
print(self.pocket_center, self.box_size)
def dock(self, score_func='vina', seed=0, mode='dock', exhaustiveness=8, save_pose=False, **kwargs): # seed=0 mean random seed
v = Vina(sf_name=score_func, seed=seed, verbosity=0, **kwargs)
v.set_receptor(self.prot_pdbqt)
v.set_ligand_from_file(self.lig_pdbqt)
v.compute_vina_maps(center=self.pocket_center, box_size=self.box_size)
if mode == 'score_only':
score = v.score()[0]
elif mode == 'minimize':
score = v.optimize()[0]
elif mode == 'dock':
v.dock(exhaustiveness=exhaustiveness, n_poses=1)
score = v.energies(n_poses=1)[0][0]
else:
raise ValueError
if not save_pose:
return score
else:
if mode == 'score_only':
pose = None
elif mode == 'minimize':
tmp = tempfile.NamedTemporaryFile()
with open(tmp.name, 'w') as f:
v.write_pose(tmp.name, overwrite=True)
with open(tmp.name, 'r') as f:
pose = f.read()
elif mode == 'dock':
pose = v.poses(n_poses=1)
else:
raise ValueError
return score, pose
class VinaDockingTask(BaseDockingTask):
@classmethod
def from_generated_data(cls, data, protein_root='./data/crossdocked', **kwargs):
# load original pdb
protein_fn = os.path.join(
os.path.dirname(data.ligand_filename),
os.path.basename(data.ligand_filename)[:10] + '.pdb' # PDBId_Chain_rec.pdb
)
protein_path = os.path.join(protein_root, protein_fn)
ligand_rdmol = reconstruct_from_generated(data.clone())
return cls(protein_path, ligand_rdmol, **kwargs)
@classmethod
def from_original_data(cls, data, ligand_root='./data/crossdocked_pocket10', protein_root='./data/crossdocked',
**kwargs):
protein_fn = os.path.join(
os.path.dirname(data.ligand_filename),
os.path.basename(data.ligand_filename)[:10] + '.pdb'
)
protein_path = os.path.join(protein_root, protein_fn)
ligand_path = os.path.join(ligand_root, data.ligand_filename)
ligand_rdmol = next(iter(Chem.SDMolSupplier(ligand_path)))
return cls(protein_path, ligand_rdmol, **kwargs)
@classmethod
def from_generated_mol(cls, ligand_rdmol, ligand_filename, protein_root='./data/crossdocked', **kwargs):
# load original pdb
protein_fn = os.path.join(
os.path.dirname(ligand_filename),
os.path.basename(ligand_filename)[:10] + '.pdb' # PDBId_Chain_rec.pdb
)
protein_path = os.path.join(protein_root, protein_fn)
return cls(protein_path, ligand_rdmol, **kwargs)
def __init__(self, protein_path, ligand_rdmol, tmp_dir='./tmp', center=None,
size_factor=1., buffer=5.0):
super().__init__(protein_path, ligand_rdmol)
# self.conda_env = conda_env
self.tmp_dir = os.path.realpath(tmp_dir)
os.makedirs(tmp_dir, exist_ok=True)
self.task_id = get_random_id()
self.receptor_id = self.task_id + '_receptor'
self.ligand_id = self.task_id + '_ligand'
self.receptor_path = protein_path
self.ligand_path = os.path.join(self.tmp_dir, self.ligand_id + '.sdf')
self.recon_ligand_mol = ligand_rdmol
ligand_rdmol = Chem.AddHs(ligand_rdmol, addCoords=True)
sdf_writer = Chem.SDWriter(self.ligand_path)
sdf_writer.write(ligand_rdmol)
sdf_writer.close()
self.ligand_rdmol = ligand_rdmol
pos = ligand_rdmol.GetConformer(0).GetPositions()
if center is None:
self.center = (pos.max(0) + pos.min(0)) / 2
else:
self.center = center
if size_factor is None:
self.size_x, self.size_y, self.size_z = 20, 20, 20
else:
self.size_x, self.size_y, self.size_z = (pos.max(0) - pos.min(0)) * size_factor + buffer
self.proc = None
self.results = None
self.output = None
self.error_output = None
self.docked_sdf_path = None
def run(self, mode='dock', exhaustiveness=8, **kwargs):
ligand_pdbqt = self.ligand_path[:-4] + '.pdbqt'
protein_pqr = self.receptor_path[:-4] + '.pqr'
protein_pdbqt = self.receptor_path[:-4] + '.pdbqt'
lig = PrepLig(self.ligand_path, 'sdf')
lig.get_pdbqt(ligand_pdbqt)
prot = PrepProt(self.receptor_path)
if not os.path.exists(protein_pqr):
prot.addH(protein_pqr)
if not os.path.exists(protein_pdbqt):
prot.get_pdbqt(protein_pdbqt)
dock = VinaDock(ligand_pdbqt, protein_pdbqt)
dock.pocket_center, dock.box_size = self.center, [self.size_x, self.size_y, self.size_z]
score, pose = dock.dock(score_func='vina', mode=mode, exhaustiveness=exhaustiveness, save_pose=True, **kwargs)
return [{'affinity': score, 'pose': pose}]
# if __name__ == '__main__':
# lig_pdbqt = 'data/lig.pdbqt'
# mol_file = 'data/1a4k_ligand.sdf'
# a = PrepLig(mol_file, 'sdf')
# # mol_file = 'CC(=C)C(=O)OCCN(C)C'
# # a = PrepLig(mol_file, 'smi')
# a.addH()
# a.gen_conf()
# a.get_pdbqt(lig_pdbqt)
#
# prot_file = 'data/1a4k_protein_chainAB.pdb'
# prot_dry = 'data/protein_dry.pdb'
# prot_pqr = 'data/protein.pqr'
# prot_pdbqt = 'data/protein.pdbqt'
# b = PrepProt(prot_file)
# b.del_water(prot_dry)
# b.addH(prot_pqr)
# b.get_pdbqt(prot_pdbqt)
#
# dock = VinaDock(lig_pdbqt, prot_pdbqt)
# dock.get_box()
# dock.dock()
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