def prep_structure(rdmol):
mb = Chem.MolToMolBlock(rdmol)
ims = oechem.oemolistream()
ims.SetFormat(oechem.OEFormat_SDF)
ims.openstring(mb)
for buf_mol in ims.GetOEMols():
oemol = oechem.OEMol(buf_mol)
omega = oeomega.OEOmega()
# omega.SetIncludeInput(True)
omega.SetMaxSearchTime(30)
omega.SetCanonOrder(False)
omega.SetSampleHydrogens(True)
eWindow = 15.0
omega.SetEnergyWindow(eWindow)
# omega.SetMaxConfs(800)
omega.SetMaxConfs(400)
omega.SetRMSThreshold(1.0)
if omega(oemol):
result = oequacpac.OEAssignCharges(oemol,
oequacpac.OEAM1BCCELF10Charges())
if result is False:
return None
else:
charges = []
for index, atom in enumerate(oemol.GetAtoms()):
q = atom.GetPartialCharge() * np.sqrt(ONE_4PI_EPS0)
charges.append(q)
return charges
else:
return None
def static_parameterize(mol):
"""
Parameters
----------
mol: Chem.ROMol
molecule to be parameterized.
"""
# imported here for optional dependency
from openeye import oechem
from openeye import oequacpac
mb = Chem.MolToMolBlock(mol)
ims = oechem.oemolistream()
ims.SetFormat(oechem.OEFormat_SDF)
ims.openstring(mb)
for buf_mol in ims.GetOEMols():
oemol = oechem.OEMol(buf_mol)
result = oequacpac.OEAssignCharges(oemol,
oequacpac.OEAM1BCCELF10Charges())
if result is False:
raise Exception('Unable to assign charges')
charges = []
for index, atom in enumerate(oemol.GetAtoms()):
q = atom.GetPartialCharge() * np.sqrt(constants.ONE_4PI_EPS0)
charges.append(q)
return np.array(charges)
def oe_assign_charges(mol, charge_model="AM1BCCELF10"):
"""assign partial charges, then premultiply by sqrt(ONE_4PI_EPS0)
as an optimization"""
# imported here for optional dependency
from openeye import oequacpac
charge_engines = {
"AM1": oequacpac.OEAM1Charges(symmetrize=True),
"AM1BCC": oequacpac.OEAM1BCCCharges(symmetrize=True),
"AM1BCCELF10": oequacpac.OEAM1BCCELF10Charges(),
}
charge_engine = charge_engines[charge_model]
oemol = convert_to_oe(mol)
result = oequacpac.OEAssignCharges(oemol, charge_engine)
if result is False:
raise Exception("Unable to assign charges")
partial_charges = np.array(
[atom.GetPartialCharge() for atom in oemol.GetAtoms()])
# https://github.com/proteneer/timemachine#forcefield-gotchas
# "The charges have been multiplied by sqrt(ONE_4PI_EPS0) as an optimization."
inlined_constant = np.sqrt(constants.ONE_4PI_EPS0)
return inlined_constant * partial_charges
def prep_structure(rdmol):
oemol = convert_to_oe(rdmol)
omega = oeomega.OEOmega()
# omega.SetIncludeInput(True)
omega.SetMaxSearchTime(30)
omega.SetCanonOrder(False)
omega.SetSampleHydrogens(True)
eWindow = 15.0
omega.SetEnergyWindow(eWindow)
# omega.SetMaxConfs(800)
omega.SetMaxConfs(400)
omega.SetRMSThreshold(1.0)
if omega(oemol):
result = oequacpac.OEAssignCharges(oemol,
oequacpac.OEAM1BCCELF10Charges())
if result is False:
return None
else:
charges = []
for index, atom in enumerate(oemol.GetAtoms()):
q = atom.GetPartialCharge() * np.sqrt(ONE_4PI_EPS0)
charges.append(q)
return charges
else:
return None
def charge_mols(infile, outfile, reffile=None):
### Read in molecules
ifs = oechem.oemolistream()
if not ifs.open(infile):
oechem.OEThrow.Warning("Unable to open %s for reading" % infile)
return
### Open output file
ofs = oechem.oemolostream()
if not ofs.open(outfile):
oechem.OEThrow.Fatal("Unable to open %s for writing" % outfile)
### Charge the molecules and write output
if reffile is None:
for mol in ifs.GetOEMols():
if not oequacpac.OEAssignCharges(mol,
oequacpac.OEAM1BCCELF10Charges()):
oechem.OEThrow.Warning("Unable to charge mol {}".format(
mol.GetTitle()))
oechem.OEWriteConstMolecule(ofs, mol)
ifs.close()
ofs.close()
else:
### Read in molecules
rfs = oechem.oemolistream()
if not rfs.open(reffile):
oechem.OEThrow.Warning("Unable to open %s for reading" % reffile)
return
### Set coordinates of desired molecule on the mol with charges
for in_mol, ref_mol in zip(ifs.GetOEMols(), rfs.GetOEMols()):
ref_mol.SetCoords(in_mol.GetCoords())
oechem.OEWriteConstMolecule(ofs, ref_mol)
ifs.close()
ofs.close()
def charge_mol(mol, omega):
"""Generate conformers and assign AM1BCCELF10 charges to mol"""
if omega(mol):
#black box function to assign charges to a molecule
oequacpac.OEAssignCharges(mol, oequacpac.OEAM1BCCELF10Charges())
else:
print("Failed to generate conformation(s) for molecule %s" %
mol.GetTitle())
def AssignChargesByName(mol, name):
if name == "noop":
return oequacpac.OEAssignCharges(mol, oequacpac.OEChargeEngineNoOp())
elif name == "mmff" or name == "mmff94":
return oequacpac.OEAssignCharges(mol, oequacpac.OEMMFF94Charges())
elif name == "am1bcc":
return oequacpac.OEAssignCharges(mol, oequacpac.OEAM1BCCCharges())
elif name == "am1bccnosymspt":
optimize = True
symmetrize = True
return oequacpac.OEAssignCharges(
mol, oequacpac.OEAM1BCCCharges(not optimize, not symmetrize))
elif name == "amber" or name == "amberff94":
return oequacpac.OEAssignCharges(mol, oequacpac.OEAmberFF94Charges())
elif name == "am1bccelf10":
return oequacpac.OEAssignCharges(mol, oequacpac.OEAM1BCCELF10Charges())
return False
def assignELF10charges(molecule, max_confs=800, strictStereo=True):
"""
This function computes atomic partial charges for an OEMol by
using the ELF10 method
Parameters:
-----------
molecule : OEMol object
The molecule that needs to be charged
max_confs : integer
The max number of conformers used to calculate the atomic partial charges
strictStereo : bool
a flag used to check if atoms need to have assigned stereo chemistry or not
Return:
-------
mol_copy : OEMol
a copy of the original molecule with assigned atomic partial charges
"""
mol_copy = molecule.CreateCopy()
# The passed molecule could have already conformers. If the conformer number
# does not exceed the max_conf threshold then max_confs conformations will
# be generated
if not mol_copy.GetMaxConfIdx() > 200:
# Generate up to max_confs conformers
mol_copy = generate_conformers(mol_copy,
max_confs=max_confs,
strictStereo=strictStereo)
# Assign MMFF Atom types
if not oechem.OEMMFFAtomTypes(mol_copy):
raise RuntimeError("MMFF atom type assignment returned errors")
# ELF10 charges
status = oequacpac.OEAssignCharges(mol_copy,
oequacpac.OEAM1BCCELF10Charges())
if not status:
raise RuntimeError("OEAssignCharges returned error code %d" % status)
return mol_copy
omega.SetStrictStereo(False)
omega.SetStrictAtomTypes(False)
omega.SetSampleHydrogens(
True
) # Word to the wise: skipping this step can lead to significantly different charges!
omega.SetEnergyWindow(15.0)
omega.SetRMSThreshold(
1.0
) # Word to the wise: skipping this step can lead to significantly different charges!
if omega(mol_multiconf): # generate conformation
# Generate am1bcc partial charges
oequacpac.OEAssignCharges(mol_multiconf,
oequacpac.OEAM1BCCELF10Charges())
# Get total charge
conf = mol_multiconf.GetConf(oechem.OEHasConfIdx(0))
absFCharge = 0
sumFCharge = 0
sumPCharge = 0.0
for atm in mol_multiconf.GetAtoms():
sumFCharge += atm.GetFormalCharge()
absFCharge += abs(atm.GetFormalCharge())
sumPCharge += atm.GetPartialCharge()
oechem.OEThrow.Info(
"%s: %d formal charges give total charge %d ; Sum of Partial Charges %5.4f"
% (mol_multiconf.GetTitle(), absFCharge, sumFCharge, sumPCharge))
# Output file
def hybrid_docking(receptor_path,
molecules_path,
docked_molecules_path,
n_poses=10):
"""Automated hybrid docking of small molecules to a receptor.
Parameters
----------
receptor_path : str
Path to PDB file containing receptor and reference ligand, or pre-prepared receptor for docking
molecules_path : str
Path to file containing one or more molecules (in OpenEye readable format) to be docked.
(For example, list of SMILES)
docked_molecules_path : str
Path to output file to be created to contain docked molecules
Uses OpenEye recognized file extension, such as .mol2 or .sdf
n_poses : int, optional, default=1
Number of docked poses to generate
receptor_filename : str, optional, default=None
If not None, the pre-prepared receptor is loaded
TODO: How can this API be improved?
"""
from .docking import create_receptor, load_receptor, pose_molecule
from openeye import oedocking, oechem
#import openmoltools as moltools # TODO: Bring these methods into this module
# Try to load pre-prepared receptor from specified file
receptor = oechem.OEGraphMol()
print('Attempting to load receptor from {}...'.format(receptor_path))
if not oedocking.OEReadReceptorFile(receptor, receptor_path):
# Load complex of receptor and reference ligand
complex_istream = oechem.oemolistream(receptor_path)
complex = oechem.OEGraphMol()
oechem.OEReadMolecule(complex_istream, complex)
# Attempt to split into components and build receptor based on reference ligand
print('Attempting to split complex into components...')
ligand = oechem.OEGraphMol()
protein = oechem.OEGraphMol()
water = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if oechem.OESplitMolComplex(ligand, protein, water, other, complex):
# Create receptor using bound ligand reference
print('Creating receptor using reference ligand...')
oedocking.OEMakeReceptor(receptor, protein, ligand)
# TODO: We can store prepared receptor file if desired
oedocking.OEWriteReceptorFile(
receptor,
'/home/guoj1/projects/INSPIRE/kinomodel/kinomodel/data/docking/prepared_receptor.oeb'
)
else:
raise Exception(
'Could not split specified PDB file {} into receptor and reference ligand'
.format(receptor_path))
# Open file for writing docked molecules
docked_molecules_ostream = oechem.oemolostream(docked_molecules_path)
# Configure omega
# From canonical recipe: https://docs.eyesopen.com/toolkits/cookbook/python/modeling/am1-bcc.html
from openeye import oeomega
omega = oeomega.OEOmega()
omega.SetIncludeInput(False)
omega.SetCanonOrder(False)
omega.SetSampleHydrogens(True)
eWindow = 15.0
omega.SetEnergyWindow(eWindow)
omega.SetMaxConfs(800)
omega.SetRMSThreshold(1.0)
# Dock all molecules requested
dock_method = oedocking.OEDockMethod_Hybrid2
dock_resolution = oedocking.OESearchResolution_Standard
dock = oedocking.OEDock(dock_method, dock_resolution)
dock.Initialize(receptor)
molecules_istream = oechem.oemolistream(molecules_path)
molecule = oechem.OEGraphMol()
for molecule in molecules_istream.GetOEMols():
print("docking", molecule.GetTitle())
#docked_molecules = pose_molecule(receptor, molecule, n_poses=n_poses)
#molecule = moltools.openeye.get_charges(molecule, keep_confs=10)
# Generate conformers
if not omega(molecule):
continue
# Apply charges
from openeye import oequacpac
oequacpac.OEAssignCharges(molecule, oequacpac.OEAM1BCCELF10Charges())
# Dock
docked_molecule = oechem.OEGraphMol()
dock.DockMultiConformerMolecule(docked_molecule, molecule)
sdtag = oedocking.OEDockMethodGetName(dock_method)
oedocking.OESetSDScore(docked_molecule, dock, sdtag)
dock.AnnotatePose(docked_molecule)
oechem.OEWriteMolecule(docked_molecules_ostream, docked_molecule)