def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s input_molecule output_molecule" % args[0])
ifs = oechem.oemolistream()
if not ifs.open(args[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[1])
ofs = oechem.oemolostream()
if not ofs.open(args[2]):
oechem.OEThrow.Fatal("Unable to open %s for writing" % args[2])
mol = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol)
opts = oeszybki.OESzybkiOptions()
opts.GetOptOptions().SetOptimizerType(oeszybki.OEOptType_NEWTON)
opts.GetSolventOptions().SetSolventModel(oeszybki.OESolventModel_Sheffield)
sz = oeszybki.OESzybki(opts)
res = oeszybki.OESzybkiResults()
if (sz(mol, res)):
oechem.OEWriteMolecule(ofs, mol)
res.Print(oechem.oeout)
return 0
def optimize_poses(
docking_poses: List[oechem.OEGraphMol],
protein: Union[oechem.OEMolBase, oechem.OEGraphMol],
) -> List[oechem.OEGraphMol]:
"""
Optimize the torsions of docking poses in a protein binding site.
Parameters
----------
docking_poses: list of oechem.OEGraphMol
The docking poses to optimize.
protein: oechem.OEGraphMol or oechem.MolBase
The OpenEye molecule holding a protein structure.
Returns
-------
optimized_docking_poses: list of oechem.OEGraphMol
The optimized docking poses.
"""
from openeye import oeszybki
options = oeszybki.OESzybkiOptions()
options.SetRunType(oeszybki.OERunType_TorsionsOpt)
options.GetProteinOptions().SetExactVdWProteinLigand(True)
options.GetProteinOptions().SetProteinElectrostaticModel(
oeszybki.OEProteinElectrostatics_ExactCoulomb)
options.GetOptOptions().SetGradTolerance(0.00001)
szybki = oeszybki.OESzybki(options)
szybki.SetProtein(protein)
optimized_docking_poses = []
for docking_pose in docking_poses:
result = oeszybki.OESzybkiResults()
szybki(docking_pose, result)
optimized_docking_poses.append(oechem.OEGraphMol(docking_pose))
return optimized_docking_poses
def QuickOpt(Mol):
"""
Fast MM optimization to whittle down number of conformers before QM.
Default Szybki OEOptType type set to steepest descent (SD) based on
preliminary comparisons.
Parameters
----------
Mol: single OEChem molecule (aka single conformer)
Returns
-------
boolean: True if completed successfully, False otherwise.
"""
# set general energy options along with the run type specification
optSzybki = oeszybki.OESzybkiOptions()
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94S)
optSzybki.SetSolventModel(oeszybki.OESolventModel_Sheffield)
optSzybki.SetOptimizerType(oeszybki.OEOptType_SD)
taglabel = 'MM Szybki SD Energy'
# generate szybki MMFF94 engine for minimization
szOpt = oeszybki.OESzybki(optSzybki)
# construct a results object to contain the results of a szybki calculation
szResults = oeszybki.OESzybkiResults()
# work on a copy of the molecule
tmpmol = oechem.OEMol(Mol)
if not szOpt(tmpmol, szResults):
print('szybki run failed for %s' % tmpmol.GetTitle())
return False
Mol.SetCoords(tmpmol.GetCoords())
oechem.OESetSDData(Mol, oechem.OESDDataPair(taglabel, "%.12f" \
% szResults.GetTotalEnergy()))
return True
def main(args=[__name__]):
if len(args) != 3:
oechem.OEThrow.Usage("%s <molfile> <outfile>" % args[0])
ifs = oechem.oemolistream()
if not ifs.open(args[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[1])
ofs = oechem.oemolostream()
if not ofs.open(args[2]):
oechem.OEThrow.Fatal("Unable to open %s for writing" % args[2])
mol = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol)
opts = oeszybki.OESzybkiOptions()
opts.GetGeneralOptions().SetForceFieldType(oeszybki.OEForceFieldType_SMIRNOFF)
sz = oeszybki.OESzybki(opts)
results = oeszybki.OESzybkiResults()
if not sz(mol, results):
return 1
oechem.OEWriteMolecule(ofs, mol)
results.Print(oechem.oeout)
return 0
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s input_molecule output_molecule" % args[0])
ifs = oechem.oemolistream()
if not ifs.open(args[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[1])
ofs = oechem.oemolostream()
if not ofs.open(args[2]):
oechem.OEThrow.Fatal("Unable to open %s for writing" % args[2])
opts = oeszybki.OESzybkiOptions()
opts.GetOptOptions().SetOptimizerType(oeszybki.OEOptType_NEWTON)
opts.GetGeneralOptions().SetForceFieldType(
oeszybki.OEForceFieldType_MMFF94S)
opts.GetSolventOptions().SetSolventModel(oeszybki.OESolventModel_Sheffield)
opts.GetSolventOptions().SetChargeEngine(oequacpac.OEChargeEngineNoOp())
sz = oeszybki.OESzybki(opts)
res = oeszybki.OESzybkiResults()
for mol in ifs.GetOEMols():
for conf in mol.GetConfs():
if sz(conf, res):
oechem.OESetSDData(
conf,
oechem.OESDDataPair('Total_energy',
"%0.4f" % res.GetTotalEnergy()))
oechem.OEWriteMolecule(ofs, mol)
ifs.close()
ofs.close()
return 0
def main(argv=[__name__]):
if len(argv) != 4:
oechem.OEThrow.Usage("%s <molfile> <protein> <outfile>" % argv[0])
lfs = oechem.oemolistream()
if not lfs.open(argv[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % argv[1])
pfs = oechem.oemolistream()
if not pfs.open(argv[2]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % argv[2])
ofs = oechem.oemolostream()
if not ofs.open(argv[3]):
oechem.OEThrow.Fatal("Unable to open %s for writing" % argv[3])
mol = oechem.OEGraphMol()
oechem.OEReadMolecule(lfs, mol)
protein = oechem.OEGraphMol()
oechem.OEReadMolecule(pfs, protein)
opts = oeszybki.OESzybkiOptions()
sz = oeszybki.OESzybki(opts)
sz.SetProtein(protein)
res = oeszybki.OESzybkiResults()
if not sz(mol, res):
return 1
oechem.OEWriteMolecule(ofs, mol)
res.Print(oechem.oeout)
return 0
def resolve_clashes(mol, clashfile):
"""
Minimize conformers with severe steric interaction.
Parameters
----------
mol : single OEChem molecule (single conformer)
clashfile : string
name of file to write output
Returns
-------
boolean
True if completed successfully, False otherwise.
"""
# set general energy options along with the single-point specification
spSzybki = oeszybki.OESzybkiOptions()
spSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94S)
spSzybki.SetSolventModel(oeszybki.OESolventModel_Sheffield)
spSzybki.SetRunType(oeszybki.OERunType_SinglePoint)
# generate the szybki MMFF94 engine for single points
szSP = oeszybki.OESzybki(spSzybki)
# construct minimiz options from single-points options to get general optns
optSzybki = oeszybki.OESzybkiOptions(spSzybki)
# now reset the option for minimization
optSzybki.SetRunType(oeszybki.OERunType_CartesiansOpt)
# generate szybki MMFF94 engine for minimization
szOpt = oeszybki.OESzybki(optSzybki)
# add strong harmonic restraints to nonHs
szOpt.SetHarmonicConstraints(10.0)
# construct a results object to contain the results of a szybki calculation
szResults = oeszybki.OESzybkiResults()
# work on a copy of the molecule
tmpmol = oechem.OEMol(mol)
if not szSP(tmpmol, szResults):
print('szybki run failed for %s' % tmpmol.GetTitle())
return False
Etotsp = szResults.GetTotalEnergy()
Evdwsp = szResults.GetEnergyTerm(oeszybki.OEPotentialTerms_MMFFVdW)
if Evdwsp > 35:
if not szOpt(tmpmol, szResults):
print('szybki run failed for %s' % tmpmol.GetTitle())
return False
Etot = szResults.GetTotalEnergy()
Evdw = szResults.GetEnergyTerm(oeszybki.OEPotentialTerms_MMFFVdW)
wfile = open(clashfile, 'a')
wfile.write('%s resolved bad clash: initial vdW: %.4f ; '
'resolved EvdW: %.4f\n' %
(tmpmol.GetTitle(), Evdwsp, Evdw))
wfile.close()
mol.SetCoords(tmpmol.GetCoords())
oechem.OESetSDData(mol, oechem.OESDDataPair('MM Szybki Single Point Energy'\
, "%.12f" % szResults.GetTotalEnergy()))
return True
def optMMFF(Mol, FF, fname):
"""
Take an OEMol, conduct an energy minimization, and write
this molecule's output to a .mol2 file.
Note: the optimization type is BFGS.
Parameters
----------
Mol: an OEChem molecule
FF: string for OEForceFieldType to use. Either "MMFF94" or "MMFF94S"
fname: string name of the output .mol2 file to save molecule.
Returns
-------
boolean True if the function successfully completed, False otherwise
"""
tmpmol = oechem.OEMol( Mol) # work on a copy of the molecule
# Open output file to write molecule.
ofs = oechem.oemolostream()
if os.path.exists(fname):
print("Output .mol2 file already exists. Skipping.\n")
return
if not ofs.open(fname):
oechem.OEThrow.Fatal("Unable to open %s for writing" % fname)
# set general energy options along with the run type specification
optSzybki = oeszybki.OESzybkiOptions()
optSzybki.SetSolventModel(oeszybki.OESolventModel_Sheffield)
optSzybki.SetOptimizerType(oeszybki.OEOptType_BFGS)
# set the particular force field
if FF == "MMFF94":
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94)
elif FF == "MMFF94S":
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94S)
else:
print( 'optMMFF failed for %s' % tmpmol.GetTitle() )
return False
# create additional dependencies, then perform opt (in if statement)
szOpt = oeszybki.OESzybki( optSzybki) # generate minimization engine
szResults = oeszybki.OESzybkiResults() # make object to hold szybki results
if not szOpt(tmpmol, szResults):
print( 'optMMFF failed for %s' % tmpmol.GetTitle() )
return False
# write out mol2 file and close the output filestream.
oechem.OEWriteConstMolecule(ofs, tmpmol)
ofs.close()
return True
def optMMFF(Mol, FF, fname, log):
"""
Take an OEMol, conduct an energy minimization, and write
this molecule's output to a .mol2 file.
Note: the optimization type is BFGS.
Parameters
----------
Mol: an OEChem molecule
FF: string for OEForceFieldType to use. Either "MMFF94" or "MMFF94S"
fname: string name of the output .mol2 file to save molecule.
Returns
-------
boolean True if the function successfully completed, False otherwise
"""
tmpmol = oechem.OEMol( Mol) # work on a copy of the molecule
if os.path.exists(fname):
log.write("Output .mol2 file already exists. Skipping.\n")
return False
# set general energy options along with the run type specification
optSzybki = oeszybki.OESzybkiOptions()
optSzybki.SetSolventModel(oeszybki.OESolventModel_NoSolv)
optSzybki.SetOptimizerType(oeszybki.OEOptType_BFGS)
# set the particular force field
if FF == "MMFF94":
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94)
elif FF == "MMFF94S":
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94S)
else:
log.write( 'optMMFF failed for %s\n' % tmpmol.GetTitle() )
return False
# create additional dependencies, then perform opt (in if statement)
szOpt = oeszybki.OESzybki( optSzybki) # generate minimization engine
szResults = oeszybki.OESzybkiResults() # make object to hold szybki results
if not szOpt(tmpmol, szResults):
log.write( 'optMMFF failed for %s\n' % tmpmol.GetTitle() )
return False
# try writing output file and return result
return writeUpdatedMol(tmpmol, fname, log)
def min_mmff94x(mol, ofs, mmff94s=False):
"""
Minimize the mol with MMFF94 or MMFF94S force field.
Parameters
----------
mol : OpenEye single-conformer molecule
ofs : OpenEye output filestream
mmff94s : Boolean
True to minimize with MMFF94S
"""
# make copy of the input mol
oe_mol = oechem.OEGraphMol(mol)
# set general energy options along with the run type specification
optSzybki = oeszybki.OESzybkiOptions()
optSzybki.SetSolventModel(oeszybki.OESolventModel_NoSolv)
optSzybki.SetOptimizerType(oeszybki.OEOptType_BFGS)
# minimize with input charges not mmff94(s) charges
# https://docs.eyesopen.com/toolkits/python/szybkitk/examples.html#optimization-of-all-conformers-of-a-ligand
optSzybki.GetSolventOptions().SetChargeEngine(oequacpac.OEChargeEngineNoOp())
# set the particular force field
if mmff94s:
sdlabel = "MMFF94S"
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94S)
else:
sdlabel = "MMFF94"
optSzybki.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94)
# generate minimization engine
szOpt = oeszybki.OESzybki(optSzybki)
# make object to hold szybki results
szResults = oeszybki.OESzybkiResults()
# perform minimization
if not szOpt(oe_mol, szResults):
smilabel = oechem.OEGetSDData(oe_mol, "SMILES QCArchive")
print( ' >>> MMFF94x minimization failed for %s\n' % smilabel )
energy = szResults.GetTotalEnergy()
# save geometry, save energy as tag, write mol to file
oechem.OESetSDData(oe_mol, f"Energy {sdlabel}", str(energy))
oechem.OEWriteConstMolecule(ofs, oe_mol)
def main(args):
if len(args) != 4:
oechem.OEThrow.Usage("%s protein input_ligand output_ligand" % args[0])
pfs = oechem.oemolistream()
if not pfs.open(args[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[1])
lfs = oechem.oemolistream()
if not lfs.open(args[2]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[2])
ofs = oechem.oemolostream()
if not ofs.open(args[3]):
oechem.OEThrow.Fatal("Unable to open %s for writing" % args[3])
mol = oechem.OEGraphMol()
protein = oechem.OEGraphMol()
oechem.OEReadMolecule(lfs, mol)
oechem.OEReadMolecule(pfs, protein)
opts = oeszybki.OESzybkiOptions()
opts.GetOptOptions().SetOptimizerType(oeszybki.OEOptType_NEWTON)
opts.GetProteinOptions().SetProteinElectrostaticModel(
oeszybki.OEProteinElectrostatics_ExactCoulomb)
opts.GetProteinOptions().SetProteinFlexibilityType(
oeszybki.OEProtFlex_Residues)
opts.GetProteinOptions().SetProteinFlexibilityRange(2.0)
sz = oeszybki.OESzybki(opts)
sz.SetProtein(protein)
res = oeszybki.OESzybkiResults()
if (sz(mol, res)):
oechem.OEWriteMolecule(ofs, mol)
res.Print(oechem.oeout)
return 0
def main(argv=[__name__]):
itf = oechem.OEInterface(Interface, argv)
ifs = oechem.oemolistream()
if not ifs.open(itf.GetString("-in")):
oechem.OEThrow.Fatal("Unable to open %s for reading" %
itf.GetString("-in"))
pfs = oechem.oemolistream()
if not pfs.open(itf.GetString("-protein")):
oechem.OEThrow.Fatal("Unable to open %s for reading",
itf.GetString("-protein"))
ofs = oechem.oemolostream()
if not ofs.open(itf.GetString("-outl")):
oechem.OEThrow.Fatal("Unable to open %s for writing" %
itf.GetString("-outl"))
opfs = oechem.oemolostream()
if not opfs.open(itf.GetString("-outp")):
oechem.OEThrow.Fatal("Unable to open %s for writing" %
itf.GetString("-outp"))
ligand = oechem.OEGraphMol()
oechem.OEReadMolecule(ifs, ligand)
protein = oechem.OEGraphMol()
oechem.OEReadMolecule(pfs, protein)
# Szybki options
opts = oeszybki.OESzybkiOptions()
opts.SetRunType(oeszybki.OERunType_CartesiansOpt)
opts.GetOptOptions().SetMaxIter(2000)
opts.GetOptOptions().SetGradTolerance(1e-6)
opts.GetGeneralOptions().SetForceFieldType(
oeszybki.OEForceFieldType_MMFF94S)
opts.GetProteinOptions().SetProteinFlexibilityType(
oeszybki.OEProtFlex_SideChainsList)
opts.GetProteinOptions().SetProteinElectrostaticModel(
oeszybki.OEProteinElectrostatics_ExactCoulomb)
res_num = []
for res in itf.GetStringList('-residues'):
intres = None
try:
intres = int(res)
except ValueError:
print('Illegal residue value: {}'.format(res))
if intres is None:
continue
res_num.append(intres)
for i in res_num:
for atom in protein.GetAtoms():
residue = oechem.OEAtomGetResidue(atom)
if (residue.GetResidueNumber() == i):
opts.AddFlexibleResidue(residue)
break
sz = oeszybki.OESzybki(opts)
sz.SetProtein(protein)
result = oeszybki.OESzybkiResults()
sz(ligand, result)
sz.GetProtein(protein)
oechem.OEWriteMolecule(opfs, protein)
oechem.OEWriteMolecule(ofs, ligand)
return 0