def main(argv):
if len(argv) != 2:
oechem.OEThrow.Usage("%s <receptor>" % argv[0])
receptor = oechem.OEGraphMol()
oedocking.OEReadReceptorFile(receptor, argv[1])
# @ <SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-1>
if oedocking.OEReceptorHasBoundLigand(receptor):
print("Receptor has a bound ligand")
else:
print("Receptor does not have bound ligand")
# @ </SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-1>
# @ <SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-2>
ligand = oechem.OEGraphMol()
if oedocking.OEReceptorHasBoundLigand(receptor):
ligand = oedocking.OEReceptorGetBoundLigand(receptor)
# @ </SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-2>
# @ <SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-3>
oedocking.OEReceptorSetBoundLigand(receptor, ligand)
# @ </SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-3>
# @ <SNIPPET-RECEPTOR-BOUND-LIGAND-EDITING-4>
oedocking.OEReceptorClearBoundLigand(receptor)
def dock_molecules_to_receptor(receptor_filename):
"""
Dock the specified molecules, writing out to specified file
Parameters
----------
receptor_filename : str
Receptor .oeb.gz filename
fragment : str
The fragment name to dock to
"""
import os
# Read the receptor
from openeye import oechem, oedocking
receptor = oechem.OEGraphMol()
if not oedocking.OEReadReceptorFile(receptor, receptor_filename):
oechem.OEThrow.Fatal("Unable to read receptor")
if not oedocking.OEReceptorHasBoundLigand(receptor):
raise Exception("Receptor does not have bound ligand")
#print('Initializing receptor...')
dockMethod = oedocking.OEDockMethod_Hybrid2
dockResolution = oedocking.OESearchResolution_Default
dock = oedocking.OEDock(dockMethod, dockResolution)
success = dock.Initialize(receptor)
# Set up Omega
#print('Expanding conformers...')
from openeye import oeomega
#omegaOpts = oeomega.OEOmegaOptions(oeomega.OEOmegaSampling_Dense)
omegaOpts = oeomega.OEOmegaOptions()
omega = oeomega.OEOmega(omegaOpts)
omega.SetStrictStereo(False)
# Dock molecules
docked_molecules = list()
for mol in molecules:
dockedMol = oechem.OEGraphMol()
# Expand conformers
omega.Build(mol)
# Dock molecule
#print(f'Docking {mol.NumConfs()} conformers...')
retCode = dock.DockMultiConformerMolecule(dockedMol, mol)
if (retCode != oedocking.OEDockingReturnCode_Success):
print("Docking Failed with error code " + oedocking.OEDockingReturnCodeGetName(retCode))
continue
# Store docking data
sdtag = oedocking.OEDockMethodGetName(dockMethod)
oedocking.OESetSDScore(dockedMol, dock, sdtag)
dock.AnnotatePose(dockedMol)
docked_molecules.append( oechem.OEMol(dockedMol) )
return docked_molecules
def dock_molecules(receptor_filename, molecules, filename):
"""
Dock the specified molecules, writing out to specified file
Parameters
----------
receptor_filename : str
Receptor .oeb.gz filename
molecules : list of openeye.oechem.OEMol
The read molecules to dock
filename : str
The filename to stream docked molecules to
"""
# Read the receptor
print('Loading receptor...')
from openeye import oechem, oedocking
receptor = oechem.OEGraphMol()
if not oedocking.OEReadReceptorFile(receptor, 'receptor.oeb.gz'):
oechem.OEThrow.Fatal("Unable to read receptor")
if oedocking.OEReceptorHasBoundLigand(receptor):
print("Receptor has a bound ligand")
else:
print("Receptor does not have bound ligand")
print('Initializing receptor...')
dockMethod = oedocking.OEDockMethod_Hybrid2
dockResolution = oedocking.OESearchResolution_High
dock = oedocking.OEDock(dockMethod, dockResolution)
success = dock.Initialize(receptor)
# Set up Omega
from openeye import oeomega
omegaOpts = oeomega.OEOmegaOptions(oeomega.OEOmegaSampling_Dense)
#omegaOpts = oeomega.OEOmegaOptions()
omega = oeomega.OEOmega(omegaOpts)
omega.SetStrictStereo(False)
# Dock molecules
with oechem.oemolostream(filename) as ofs:
from tqdm import tqdm
for mol in tqdm(molecules):
dockedMol = oechem.OEGraphMol()
# Expand conformers
omega.Build(mol)
# Dock molecule
retCode = dock.DockMultiConformerMolecule(dockedMol, mol)
if (retCode != oedocking.OEDockingReturnCode_Success):
oechem.OEThrow.Fatal("Docking Failed with error code " + oedocking.OEDockingReturnCodeGetName(retCode))
# Store docking data
sdtag = oedocking.OEDockMethodGetName(dockMethod)
oedocking.OESetSDScore(dockedMol, dock, sdtag)
dock.AnnotatePose(dockedMol)
# Write molecule
oechem.OEWriteMolecule(ofs, dockedMol)
def get_receptor(receptor_file=None, use_hybrid=True, high_resolution=True):
"""
:param receptor_file: file to .oeb or oeb.gz with prepared protein receptor
:param use_hybrid: whether or not to override using hybrid docking method
:param high_resolution: set resolution for search
:return: docking objector from OE, the receptor oemol
"""
from . import dock_conf
from openeye import oedocking
receptor = dock_conf.PrepareReceptorFromBinary(receptor_file)
if oedocking.OEReceptorHasBoundLigand(receptor) and use_hybrid:
dock_method = oedocking.OEDockMethod_Hybrid
else:
dock_method = oedocking.OEDockMethod_Chemgauss4
if high_resolution:
reso = oedocking.OESearchResolution_High
else:
reso = oedocking.OESearchResolution_Default
dock = oedocking.OEDock(dock_method, reso)
dock.Initialize(receptor)
return dock, receptor
def receptor_from_file(receptor_filename):
receptor = oechem.OEGraphMol()
if not oedocking.OEReadReceptorFile(receptor, receptor_filename):
oechem.OEThrow.Fatal("Unable to read receptor")
if not oedocking.OEReceptorHasBoundLigand(receptor):
raise Exception("Receptor does not have bound ligand")
return receptor
def begin(self):
receptor = oechem.OEGraphMol()
self.args.receptor = utils.download_dataset_to_file(self.args.receptor)
if not oedocking.OEReadReceptorFile(receptor, str(self.args.receptor)):
raise Exception("Unable to read receptor from {0}".format(self.args.receptor))
# Initialize Docking
dock_method = oedocking.OEDockMethod_Hybrid
if not oedocking.OEReceptorHasBoundLigand(receptor):
oechem.OEThrow.Warning("No bound ligand, switching OEDockMethod to ChemGauss4.")
dock_method = oedocking.OEDockMethod_Chemgauss4
dock_resolution = oedocking.OESearchResolution_Default
self.sdtag = oedocking.OEDockMethodGetName(dock_method)
self.dock = oedocking.OEDock(dock_method, dock_resolution)
if not self.dock.Initialize(receptor):
raise Exception("Unable to initialize Docking with {0}".format(self.args.receptor))
def dock_molecule(receptor, molecule_smiles, n_conformations=10, n_poses=2):
"""Run the multi-conformer docker.
Parameters
----------
receptor : openeye.oedocking.OEReceptor
The openeye receptor.
molecule_smiles : str
The SMILES string of the molecule.
n_conformations : int, optional
The number of omega conformations to pass to the multi-conformer
docker (default is 10).
n_poses : int, optional
Number of binding poses to return.
Returns
-------
docked_oemol : openeye.oechem.OEMol
The docked multi-conformer OpenEye molecule.
"""
from openeye import oechem, oedocking
import openmoltools as moltools
if oedocking.OEReceptorHasBoundLigand(receptor):
dock = oedocking.OEHybrid(oedocking.OEDockMethod_Hybrid2,
oedocking.OESearchResolution_High)
else:
dock = oedocking.OEDock()
dock.Initialize(receptor)
molecule_oemol = moltools.openeye.smiles_to_oemol(molecule_smiles)
molecule_oemol = moltools.openeye.get_charges(molecule_oemol,
keep_confs=n_conformations)
docked_oemol = oechem.OEMol()
dock.DockMultiConformerMolecule(docked_oemol, molecule_oemol, n_poses)
return docked_oemol
def dock_molecule_to_receptor(molecule, receptor_filename, covalent=False):
"""
Dock the specified molecules, writing out to specified file
Parameters
----------
molecule : oechem.OEMol
The molecule to dock
receptor_filename : str
Receptor to dock to
covalent : bool, optional, default=False
If True, try to place covalent warheads in proximity to CYS145
Returns
-------
docked_molecule : openeye.oechem.OEMol
Returns the best tautomer/protomer in docked geometry, annotated with docking score
None is returned if no viable docked pose found
"""
import os
# Extract the fragment name for the receptor
fragment = extract_fragment_from_filename(receptor_filename)
# Read the receptor
from openeye import oechem, oedocking
receptor = oechem.OEGraphMol()
if not oedocking.OEReadReceptorFile(receptor, receptor_filename):
oechem.OEThrow.Fatal("Unable to read receptor")
#print(f'Receptor has {receptor.NumAtoms()} atoms')
if not oedocking.OEReceptorHasBoundLigand(receptor):
raise Exception("Receptor does not have bound ligand")
#print('Initializing receptor...')
dockMethod = oedocking.OEDockMethod_Hybrid2
dockResolution = oedocking.OESearchResolution_High
dock = oedocking.OEDock(dockMethod, dockResolution)
success = dock.Initialize(receptor)
# Add covalent restraint if specified
warheads_found = find_warheads(molecule)
if covalent and len(warheads_found) > 0:
warheads_found = set(warheads_found.keys())
# Initialize covalent constraints
customConstraints = oedocking.OEReceptorGetCustomConstraints(receptor)
# Find CYS145 SG atom
hv = oechem.OEHierView(receptor)
hres = hv.GetResidue("A", "CYS", 145)
proteinHeavyAtom = None
for atom in hres.GetAtoms():
if atom.GetName().strip() == 'SG':
proteinHeavyAtom = atom
break
if proteinHeavyAtom is None:
raise Exception('Could not find CYS145 SG')
# Add the constraint
feature = customConstraints.AddFeature()
feature.SetFeatureName("CYS145 proximity")
for warhead_type in warheads_found:
smarts = covalent_warhead_smarts[warhead_type]
print(f'Adding constraint for SMARTS pattern {smarts}')
feature.AddSmarts(smarts)
sphereRadius = 4.0 # Angstroms
sphereCenter = oechem.OEFloatArray(3)
receptor.GetCoords(proteinHeavyAtom, sphereCenter)
sphere = feature.AddSphere()
sphere.SetRad(sphereRadius)
sphere.SetCenter(sphereCenter[0], sphereCenter[1], sphereCenter[2])
oedocking.OEReceptorSetCustomConstraints(receptor, customConstraints)
# Enumerate tautomers
from openeye import oequacpac
tautomer_options = oequacpac.OETautomerOptions()
tautomer_options.SetMaxTautomersGenerated(4096)
tautomer_options.SetMaxTautomersToReturn(16)
tautomer_options.SetCarbonHybridization(True)
tautomer_options.SetMaxZoneSize(50)
tautomer_options.SetApplyWarts(True)
pKa_norm = True
tautomers = [ oechem.OEMol(tautomer) for tautomer in oequacpac.OEGetReasonableTautomers(molecule, tautomer_options, pKa_norm) ]
# Set up Omega
#print('Expanding conformers...')
from openeye import oeomega
#omegaOpts = oeomega.OEOmegaOptions(oeomega.OEOmegaSampling_Dense)
omegaOpts = oeomega.OEOmegaOptions()
#omegaOpts.SetMaxConfs(5000)
omegaOpts.SetMaxSearchTime(60.0) # time out
omega = oeomega.OEOmega(omegaOpts)
omega.SetStrictStereo(False) # enumerate sterochemistry if uncertain
# Dock tautomers
docked_molecules = list()
from tqdm import tqdm
for mol in tautomers:
dockedMol = oechem.OEGraphMol()
# Expand conformers
omega.Build(mol)
# Dock molecule
retCode = dock.DockMultiConformerMolecule(dockedMol, mol)
if (retCode != oedocking.OEDockingReturnCode_Success):
#print("Docking Failed with error code " + oedocking.OEDockingReturnCodeGetName(retCode))
continue
# Store docking data
sdtag = oedocking.OEDockMethodGetName(dockMethod)
oedocking.OESetSDScore(dockedMol, dock, sdtag)
oechem.OESetSDData(dockedMol, "docked_fragment", fragment)
dock.AnnotatePose(dockedMol)
docked_molecules.append( dockedMol.CreateCopy() )
if len(docked_molecules) == 0:
return None
# Select the best-ranked molecule and pose
# Note that this ignores protonation state and tautomer penalties
docked_molecules.sort(key=score)
best_molecule = docked_molecules[0]
return best_molecule
