Examples: Working with Szybki TK¶
The basic Szybki TK API is provided to the users in the OESzybki,
OESzybkiOptions, OESzybkiResults and
OESzybkiEnsembleResults classes. In addition, when the purpose is to
calculate compound properties, such as solvation free energy or free energy of
selecting specific conformations out of the ensemble, the higher level API are defined in
the free functions, OEEstimateSolvFreeEnergy
and
OEEstimateConfFreeEnergies
.
Ligand Energetics and Optimization¶
Single ligand in vacuum¶
The following example illustrates how to optimize a single ligand in vacuum. As one
can see assuming a molecule is successfully read, only two objects are needed to
perform the optimization: OESzybki and OESzybkiResults.
The latter is passed as the second parameter to the parenthesis operator
OESzybki.operator()
. Molecule with the optimized coordinates is
returned as a first parameter. Optimization is done using the default MMFF94. Final
energy results are available as SD tags in the returned molecule and optionally with
a call of a method OESzybkiResults.Print
.
Listing 1: Simple Ligand in a Vacuum
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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()
sz = oeszybki.OESzybki(opts)
results = oeszybki.OESzybkiResults()
if not sz(mol, results):
return 1
oechem.OEWriteMolecule(ofs, mol)
results.Print(oechem.oeout)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Single ligand in vacuum using SMIRNOFF¶
The following example illustrates how to optimize a single ligand in vacuum using
SMIRNOFF (see SMIRNOFF). Only two objects are needed to perform
the optimization: OESzybki and OESzybkiResults.
The latter is passed as the second parameter to the parenthesis operator
OESzybki.operator()
. Partial charges have to be preassigned to the
input molecule. Molecule with the optimized coordinates is returned as a first parameter.
Final energy results are available as SD tags in the returned molecule and optionally
with a call of a method OESzybkiResults.Print
.
Listing 2: Simple Ligand in a Vacuum Using SMIRNOFF
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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_SMIRNOFF99FROSST)
sz = oeszybki.OESzybki(opts)
results = oeszybki.OESzybkiResults()
if not sz(mol, results):
return 1
oechem.OEWriteMolecule(ofs, mol)
results.Print(oechem.oeout)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a set of ligands¶
The next example illustrates the usage of Szybki TK to optimize a set of compounds with the MMFF94 force field in vacuum or in solution using Sheffield solvation model. Optionally attractive VdW can be removed. The optimization is done by default in full Cartesian coordinates, however torsion space optimization or single point calculation could be done too. A group of atoms which belong to specified SMARTS pattern might be excluded from optimization so their positions will be fixed at their initial coordinates. Note that the OESzybki object is made with a constructor which takes the instance of the OESzybkiOptions class.
Listing 3: Optimization of a Set of Ligands
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
itf = oechem.OEInterface()
if not SetupInterface(argv, itf):
return 1
ifs = oechem.oemolistream()
if not ifs.open(itf.GetString("-in")):
oechem.OEThrow.Fatal("Unable to open %s for reading" % itf.GetString("-in"))
ofs = oechem.oemolostream()
if not ofs.open(itf.GetString("-out")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-out"))
logfile = oechem.oeout
if itf.HasString("-log"):
if not logfile.open(itf.GetString("-log")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-log"))
# Szybki options
opts = oeszybki.OESzybkiOptions()
# select run type
if itf.GetBool("-t"):
opts.SetRunType(oeszybki.OERunType_TorsionsOpt)
if itf.GetBool("-n"):
opts.SetRunType(oeszybki.OERunType_SinglePoint)
# apply solvent model
if itf.GetBool("-s"):
opts.GetSolventOptions().SetSolventModel(oeszybki.OESolventModel_Sheffield)
# remove attractive VdW forces
if itf.GetBool("-a"):
opts.GetGeneralOptions().SetRemoveAttractiveVdWForces(True)
# Szybki object
sz = oeszybki.OESzybki(opts)
# fix atoms
if itf.HasString("-f"):
if not sz.FixAtoms(itf.GetString("-f")):
oechem.OEThrow.Warning("Failed to fix atoms for %s" % itf.GetString("-f"))
# process molecules
mol = oechem.OEMol()
while oechem.OEReadMolecule(ifs, mol):
logfile.write("\nMolecule %s\n" % mol.GetTitle())
no_res = True
for results in sz(mol):
results.Print(logfile)
no_res = False
if no_res:
oechem.OEThrow.Warning("No results processing molecule: %s" % mol.GetTitle())
continue
else:
oechem.OEWriteMolecule(ofs, mol)
return 0
InterfaceData = """
!PARAMETER -in
!TYPE string
!REQUIRED true
!BRIEF Input molecule file name.
!END
!PARAMETER -out
!TYPE string
!REQUIRED true
!BRIEF Output molecule file name.
!END
!PARAMETER -log
!TYPE string
!REQUIRED false
!BRIEF Log file name. Defaults to standard out.
!END
!PARAMETER -s
!TYPE bool
!DEFAULT false
!REQUIRED false
!BRIEF Optimization in solution.
!END
!PARAMETER -t
!TYPE bool
!DEFAULT false
!REQUIRED false
!BRIEF Optimization of torsions.
!END
!PARAMETER -n
!TYPE bool
!DEFAULT false
!REQUIRED false
!BRIEF Single point calculation.
!END
!PARAMETER -a
!TYPE bool
!DEFAULT false
!REQUIRED false
!BRIEF No attractive VdW forces.
!END
!PARAMETER -f
!TYPE string
!REQUIRED false
!BRIEF SMARTS pattern of fixed atoms.
!END
"""
def SetupInterface(argv, itf):
oechem.OEConfigure(itf, InterfaceData)
if oechem.OECheckHelp(itf, argv):
return False
if not oechem.OEParseCommandLine(itf, argv):
return False
if not oechem.OEIsReadable(oechem.OEGetFileType(
oechem.OEGetFileExtension(itf.GetString("-in")))):
oechem.OEThrow.Warning("%s is not a readable input file" % itf.GetString("-in"))
return False
if not oechem.OEIsWriteable(oechem.OEGetFileType(
oechem.OEGetFileExtension(itf.GetString("-out")))):
oechem.OEThrow.Warning("%s is not a writable output file" % itf.GetString("-out"))
return False
return True
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a single ligand with the Newton-Raphson method¶
The next example in this section shows how to use Newton-Raphson optimization method, rather than the default BFGS:
Listing 4: Optimization of a Single Ligand with the Newton-Raphson Method
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of all conformers of a ligand¶
Finally, the last example in this section shows how to use Newton-Raphson optimization method on all conformers of a ligand. The current charges of the ligand are used and will not be changed during the optimization.
Listing 5: Optimization of All Conformers of a Ligand
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oequacpac
from openeye import oeszybki
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
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a single bound ligand¶
The simplest case is illustrated below.
Notice the usage of the method OESzybki.SetProtein
which tells Szybki
that the ligand is placed inside the protein. Since no protein-ligand electrostatics have been
specified, neither the coordinates types which should be used by the optimizer, the code below
performs the optimization for a rigid ligand using 6 translational-rotational coordinates in
the MMFF94 VdW potential field.
Listing 5: Optimization of a Single Bound Ligand
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Protein-Ligand Energetics and Optimization¶
Examples in this section show how to optimize a bound ligand.
Optimization of a set of bound ligands in a rigid receptor¶
The next example illustrates the usage of Szybki TK to optimize a set of ligands with MMFF94 force
field inside a protein receptor. By default only VdW protein-ligand interaction is used.
Optionally exact or grid Coulomb potential as well as PB solvent screening potentials could be added.
When grid potential is selected (either Coulomb or PB) optionally it could be saved or read in when
the corresponding grid file is present in the specified directory. Notice that when the exact
Coulomb electrostatics is chosen, also the exact VdW potential is chosen (method
OESzybkiProteinOptions.SetExactVdWProteinLigand
) which allows for tight gradients
convergence (methods OESzybkiOptOptions.SetMaxIter
and OESzybkiOptOptions.SetGradTolerance
). By default ligand is treated as
a solid body, that is only its translational and rotational degrees of freedom are optimized. Optionally
also torsional degrees could be optimized. In this example protein receptor is rigid. Molecular input
file should contain initial 3D coordinates of molecules in any format supported by OEChem TK. Output
file is specified with the -out flag. In addition a log file containing energy data terms values is
written to stdout or a file specified by -log.
Listing 6: Optimization of a Set of Bound Ligands in a Rigid Receptor
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
itf = oechem.OEInterface(Interface, argv)
lfs = oechem.oemolistream()
if not lfs.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("-p")):
oechem.OEThrow.Fatal("Unable to open %s for reading", itf.GetString("-p"))
ofs = oechem.oemolostream()
if not ofs.open(itf.GetString("-out")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-out"))
logfile = oechem.oeout
if itf.HasString("-log"):
if not logfile.open(itf.GetString("-log")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-log"))
# Szybki options
opts = oeszybki.OESzybkiOptions()
# select optimization type
if(itf.GetBool("-t")):
opts.SetRunType(oeszybki.OERunType_TorsionsOpt)
else:
opts.SetRunType(oeszybki.OERunType_CartesiansOpt)
# select protein-electrostatic model
emodel = itf.GetString("-e")
elecModel = oeszybki.OEProteinElectrostatics_NoElectrostatics
if emodel == "VdW":
elecModel = oeszybki.OEProteinElectrostatics_NoElectrostatics
elif emodel == "PB":
elecModel = oeszybki.OEProteinElectrostatics_GridPB
elif emodel == "Coulomb":
elecModel = oeszybki.OEProteinElectrostatics_GridCoulomb
elif emodel == "ExactCoulomb":
elecModel = oeszybki.OEProteinElectrostatics_ExactCoulomb
opts.GetProteinOptions().SetExactVdWProteinLigand(True)
opts.GetOptOptions().SetMaxIter(1000)
opts.GetOptOptions().SetGradTolerance(1e-6)
opts.GetProteinOptions().SetProteinElectrostaticModel(elecModel)
# Szybki object
sz = oeszybki.OESzybki(opts)
# read and setup protein
protein = oechem.OEGraphMol()
oechem.OEReadMolecule(pfs, protein)
sz.SetProtein(protein)
# save or load grid potential
if(emodel == "PB" or emodel == "Coulomb"):
if(itf.HasString("-s")):
sz.SavePotentialGrid(itf.GetString("-s"))
if(itf.HasString("-l")):
sz.LoadPotentialGrid(itf.GetString("-l"))
# process molecules
for mol in lfs.GetOEMols():
logfile.write("\nMolecule %s\n" % mol.GetTitle())
no_res = True
for res in sz(mol):
res.Print(logfile)
no_res = False
if no_res:
oechem.OEThrow.Warning("No results processing molecule: %s" % mol.GetTitle())
continue
else:
oechem.OEWriteMolecule(ofs, mol)
return 0
Interface = """
!PARAMETER -in
!TYPE string
!REQUIRED true
!BRIEF Input molecule file name.
!END
!PARAMETER -p
!TYPE string
!REQUIRED true
!BRIEF Input protein file name.
!END
!PARAMETER -out
!TYPE string
!REQUIRED true
!BRIEF Output molecule file name.
!END
!PARAMETER -log
!TYPE string
!REQUIRED false
!BRIEF Log file name. Defaults to standard out.
!END
!PARAMETER -e
!TYPE string
!DEFAULT VdW
!LEGAL_VALUE VdW
!LEGAL_VALUE PB
!LEGAL_VALUE Coulomb
!LEGAL_VALUE ExactCoulomb
!BRIEF Protein ligand electrostatic model.
!END
!PARAMETER -t
!TYPE bool
!DEFAULT false
!REQUIRED false
!BRIEF Torsions added to the optimized variables.
!END
!PARAMETER -l
!TYPE string
!REQUIRED false
!BRIEF File name of the potential grid to be read.
!END
!PARAMETER -s
!TYPE string
!REQUIRED false
!BRIEF File name of the potential grid to be saved.
!END
"""
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a set of bound ligands in a partially flexible receptor¶
The next example is very similar with respect to the previous one, but the side chains of the
protein which are within the specified range from the ligand, are made flexible during optimization
(methods OESzybkiProteinOptions.SetProteinFlexibilityType
and
OESzybkiProteinOptions.SetProteinFlexibilityRange
). Optionally, partially optimized
structure can be saved to a file.
Listing 7: Optimization of a Set of Bound Ligands in a Partially Flexible Receptor
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
itf = oechem.OEInterface(Interface, argv)
lfs = oechem.oemolistream()
if not lfs.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("-p")):
oechem.OEThrow.Fatal("Unable to open %s for reading", itf.GetString("-p"))
olfs = oechem.oemolostream()
if not olfs.open(itf.GetString("-out")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-out"))
opfs = oechem.oemolostream()
if itf.HasString("-s"):
if not opfs.open(itf.GetString("-s")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-s"))
logfile = oechem.oeout
if itf.HasString("-log"):
if not logfile.open(itf.GetString("-log")):
oechem.OEThrow.Fatal("Unable to open %s for writing" % itf.GetString("-log"))
# Szybki options
opts = oeszybki.OESzybkiOptions()
# select optimization type
opt = itf.GetString("-opt")
if opt == "Cartesian":
opts.SetRunType(oeszybki.OERunType_CartesiansOpt)
if opt == "Torsion":
opts.SetRunType(oeszybki.OERunType_TorsionsOpt)
if opt == "SolidBody":
opts.SetRunType(oeszybki.OERunType_SolidBodyOpt)
# select protein-electrostatic model
emodel = itf.GetString("-e")
elecModel = oeszybki.OEProteinElectrostatics_NoElectrostatics
if emodel == "VdW":
elecModel = oeszybki.OEProteinElectrostatics_NoElectrostatics
elif emodel == "PB":
elecModel = oeszybki.OEProteinElectrostatics_GridPB
elif emodel == "Coulomb":
elecModel = oeszybki.OEProteinElectrostatics_GridCoulomb
elif emodel == "ExactCoulomb":
elecModel = oeszybki.OEProteinElectrostatics_ExactCoulomb
opts.GetProteinOptions().SetProteinElectrostaticModel(elecModel)
# use smooth potential and tight convergence
if (emodel == "VdW" or emodel == "ExactCoulomb"):
opts.GetProteinOptions().SetExactVdWProteinLigand(True)
opts.GetOptOptions().SetMaxIter(1000)
opts.GetOptOptions().SetGradTolerance(1e-6)
# protein flexibility
opts.GetProteinOptions().SetProteinFlexibilityType(oeszybki.OEProtFlex_SideChains)
opts.GetProteinOptions().SetProteinFlexibilityRange(itf.GetDouble("-d"))
# Szybki object
sz = oeszybki.OESzybki(opts)
# read and setup protein
protein = oechem.OEGraphMol()
oprotein = oechem.OEGraphMol() # optimized protein
oechem.OEReadMolecule(pfs, protein)
sz.SetProtein(protein)
# process molecules
for mol in lfs.GetOEMols():
logfile.write("\nMolecule %s\n" % mol.GetTitle())
for res in sz(mol):
res.Print(logfile)
oechem.OEWriteMolecule(olfs, mol)
if itf.HasString("-s"):
sz.GetProtein(oprotein)
oechem.OEWriteMolecule(opfs, oprotein)
return 0
Interface = """
!BRIEF -in input_molecule -p protein -out output_molecule
!PARAMETER -in
!TYPE string
!REQUIRED true
!BRIEF Input molecule file name.
!END
!PARAMETER -p
!TYPE string
!REQUIRED true
!BRIEF Input protein file name.
!END
!PARAMETER -out
!TYPE string
!REQUIRED true
!BRIEF Output molecule file name.
!END
!PARAMETER -log
!TYPE string
!REQUIRED false
!BRIEF Log file name. Defaults to standard out.
!END
!PARAMETER -e
!TYPE string
!DEFAULT VdW
!LEGAL_VALUE VdW
!LEGAL_VALUE PB
!LEGAL_VALUE Coulomb
!LEGAL_VALUE ExactCoulomb
!BRIEF Protein ligand electrostatic model.
!END
!PARAMETER -opt
!TYPE string
!DEFAULT Cartesian
!LEGAL_VALUE Cartesian
!LEGAL_VALUE Torsion
!LEGAL_VALUE SolidBody
!BRIEF Optimization method
!END
!PARAMETER -d
!TYPE double
!DEFAULT 5.0
!BRIEF Distance criteria from protein side-chains flexibility.
!END
!PARAMETER -s
!TYPE string
!REQUIRED false
!BRIEF File name the partially optimized protein will be saved.
!END
"""
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a bound ligand in a partially flexible receptor¶
The next example is very similar with respect to the previous one, but the list of
residue numbers of the protein that are made flexible during optimization is specified
by the -residues
flag (see method OESzybkiProteinOptions.AddFlexibleResidue
).
Partially optimized ligand and protein structures are saved to files specified by the
-outl
and -outp
flags, respectively.
Listing 8: Optimization of a Bound Ligand in a Partially Flexible Feceptor
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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
Interface = """
!BRIEF -in ligand -protein protein -outl output_ligand -outp output_protein -residues r1 r2 ... rn
!PARAMETER -in
!TYPE string
!REQUIRED true
!BRIEF Input ligand file name.
!END
!PARAMETER -protein
!TYPE string
!REQUIRED true
!BRIEF Input protein file name.
!END
!PARAMETER -outl
!TYPE string
!REQUIRED true
!BRIEF Output ligand file name.
!END
!PARAMETER -outp
!TYPE string
!REQUIRED true
!BRIEF Output protein file name.
!END
!PARAMETER -residues
!TYPE string
!LIST true
!REQUIRED true
!BRIEF List of residues numbers to be optimized along with the ligand
!END
"""
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Estimation of PB binding for a set of ligands¶
This example shows how to fast estimate binding for a set of ligands using PB electrostatics. Two OESzybki objects are instantiated: one for the optimization of bound ligands in VdW-Coulomb potential, and the second one which performs single-point PB calculations. Final results are attached as SD tags to the output molecules.
Listing 9: Estimation of PB Binding for a Set of Ligands
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 4:
oechem.OEThrow.Usage("%s ligand_file protein_file output_file (SDF or OEB)" % args[0])
lfs = oechem.oemolistream()
if not lfs.open(args[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % args[1])
pfs = oechem.oemolistream()
if not pfs.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])
if not oechem.OEIsSDDataFormat(ofs.GetFormat()):
oechem.OEThrow.Fatal("Output file does not support SD data used by this example")
# Szybki options for VdW-Coulomb calculations
optsC = oeszybki.OESzybkiOptions()
optsC.GetProteinOptions().SetProteinElectrostaticModel(
oeszybki.OEProteinElectrostatics_ExactCoulomb)
optsC.SetRunType(oeszybki.OERunType_CartesiansOpt)
# Szybki options for PB calculations
optsPB = oeszybki.OESzybkiOptions()
optsPB.GetProteinOptions().SetProteinElectrostaticModel(
oeszybki.OEProteinElectrostatics_SolventPBForces)
optsPB.SetRunType(oeszybki.OERunType_SinglePoint)
# Szybki objects
szC = oeszybki.OESzybki(optsC)
szPB = oeszybki.OESzybki(optsPB)
# read and setup protein
protein = oechem.OEGraphMol()
oechem.OEReadMolecule(pfs, protein)
szC.SetProtein(protein)
szPB.SetProtein(protein)
terms = set([oeszybki.OEPotentialTerms_ProteinLigandInteraction,
oeszybki.OEPotentialTerms_VdWProteinLigand,
oeszybki.OEPotentialTerms_CoulombProteinLigand,
oeszybki.OEPotentialTerms_ProteinDesolvation,
oeszybki.OEPotentialTerms_LigandDesolvation,
oeszybki.OEPotentialTerms_SolventScreening])
# process molecules
for mol in lfs.GetOEMols():
# optimize mol
if not list(szC(mol)):
oechem.OEThrow.Warning("No results processing molecule: %s" % mol.GetTitle())
continue
# do single point with better electrostatics
for conf, results in zip(mol.GetConfs(), szPB(mol)):
for i in terms:
strEnergy = ("%9.4f" % results.GetEnergyTerm(i))
oechem.OEAddSDData(conf, oeszybki.OEGetEnergyTermName(i), strEnergy)
oechem.OEWriteMolecule(ofs, mol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of a bound ligand using Newton-Raphson method¶
The last example in this section illustrates how to use SzybkiTK to optimize a ligand in partially flexible protein with Newton-Raphson optimization method.
Listing 10: Optimization of a Bound Ligand Using Newton-Raphson Method
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
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
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
DU Protein-Ligand Optimization with FF14SB-Parsley¶
Examples in this section show how to optimize a ligand in the protein active site using the OEFixedProteinLigandOptimizer and the OEFlexProteinLigandOptimizer classes. Both of these classes allow use of the FF14SB-Parsley forcefield, along with the MMFF and the MMFF-AMBER forcefields. These examples also demonstrate how to use design units as a source for the protein or the ligand. The first example optimizes an external ligand in a protein active site from a design unit, and the second example uses both the ligand and the protein from the same design unit.
Optimization of ligand in a rigid active site¶
This examples shows how to optimize a series of ligands in a rigid active site. The active site input is taken from a OEDesignUnit.
Listing 11: Optimization of Ligand in a Rigid Active Site
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
szOpts = oeszybki.OEProteinLigandOptOptions()
opts = oechem.OERefInputAppOptions(szOpts, "OptimizeLigandInDU", oechem.OEFileStringType_Mol3D,
oechem.OEFileStringType_Mol3D, oechem.OEFileStringType_DU, "-du")
if oechem.OEConfigureOpts(opts, argv, False) == oechem.OEOptsConfigureStatus_Help:
return 0
szOpts.UpdateValues(opts)
ifs = oechem.oemolistream()
if not ifs.open(opts.GetInFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetInFile())
rfs = oechem.oeifstream()
if not rfs.open(opts.GetRefFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetRefFile())
ofs = oechem.oemolostream()
if not ofs.open(opts.GetOutFile()):
oechem.OEThrow.Fatal("Unable to open %s for writing" % opts.GetOutFile())
du = oechem.OEDesignUnit()
if not oechem.OEReadDesignUnit(rfs, du):
oechem.OEThrow.Fatal("Failed to read design unit")
optimizer = oeszybki.OEFixedProteinLigandOptimizer(szOpts)
optimizer.SetProtein(du, oechem.OEDesignUnitComponents_Protein)
for mol in ifs.GetOEMols():
oechem.OEThrow.Info("Title: %s" % mol.GetTitle())
conf = 0
for res in optimizer.Optimize(mol):
conf += 1
if res.GetReturnCode() == oeszybki.OESzybkiReturnCode_Success:
oechem.OEThrow.Info("Conformer: %d" % conf)
initEne = res.GetInitialEnergies()
oechem.OEThrow.Info("Initial energies:")
oechem.OEThrow.Info(" Ligand: %0.2f" % initEne.GetLigandEnergy())
oechem.OEThrow.Info(" Intermolecular: %0.2f" % initEne.GetInterEnergy())
oechem.OEThrow.Info(" Total: %0.2f" % initEne.GetTotalEnergy())
finalEne = res.GetFinalEnergies()
oechem.OEThrow.Info("Final energies:")
oechem.OEThrow.Info(" Ligand: %0.2f" % finalEne.GetLigandEnergy())
oechem.OEThrow.Info(" Intermolecular: %0.2f" % finalEne.GetInterEnergy())
oechem.OEThrow.Info(" Total: %0.2f" % finalEne.GetTotalEnergy())
else:
oechem.OEThrow.Warning("Failed: %s" % oeszybki.OEGetSzybkiError(res.GetReturnCode()))
oechem.OEWriteMolecule(ofs, mol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Optimization of ligand in a partially flexible active site¶
This examples shows how to optimize a ligand in a partially flexible active site. In this example, both the ligand and the active site is taken from a single OEDesignUnit.
Listing 12: Optimization of Ligand in a Rigid Active Site
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
class MyOptions(oechem.OEOptions):
def __init__(self):
oechem.OEOptions.__init__(self, "MyOption")
self._optOpts = oeszybki.OEProteinLigandOptOptions()
self._flexOpts = oeszybki.OEProteinFlexOptions()
self.AddOption(self._optOpts)
self.AddOption(self._flexOpts)
pass
def CreateCopy(self):
return self
def GetOptOptions(self):
return self._optOpts
def GetFlexOptions(self):
return self._flexOpts
def main(argv=[__name__]):
myOpts = MyOptions()
opts = oechem.OESimpleAppOptions(myOpts, "OptimizeDU", oechem.OEFileStringType_DU, oechem.OEFileStringType_DU)
if oechem.OEConfigureOpts(opts, argv, False) == oechem.OEOptsConfigureStatus_Help:
return 0
optOpts = myOpts.GetOptOptions()
flexOpts = myOpts.GetFlexOptions()
optOpts.UpdateValues(opts)
flexOpts.UpdateValues(opts)
ifs = oechem.oeifstream()
if not ifs.open(opts.GetInFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetInFile())
ofs = oechem.oeofstream()
if not ofs.open(opts.GetOutFile()):
oechem.OEThrow.Fatal("Unable to open %s for writing" % opts.GetOutFile())
optimizer = oeszybki.OEFlexProteinLigandOptimizer(optOpts)
du = oechem.OEDesignUnit()
while oechem.OEReadDesignUnit(ifs, du):
oechem.OEThrow.Info("Title: %s" % du.GetTitle())
res = oeszybki.OEProteinLigandOptResults()
proteinMask = oechem.OEDesignUnitComponents_Protein
retCode = optimizer.Optimize(res, du, proteinMask, oechem.OEDesignUnitComponents_Ligand, flexOpts)
if retCode == oeszybki.OESzybkiReturnCode_Success:
initEne = res.GetInitialEnergies()
oechem.OEThrow.Info("Initial energies:")
oechem.OEThrow.Info(" Ligand: %0.2f" % initEne.GetLigandEnergy())
oechem.OEThrow.Info(" Flexible Protein: %0.2f" % initEne.GetHostEnergy())
oechem.OEThrow.Info(" Intermolecular: %0.2f" % initEne.GetInterEnergy())
oechem.OEThrow.Info(" Total: %0.2f" % initEne.GetTotalEnergy())
finalEne = res.GetFinalEnergies()
oechem.OEThrow.Info("Final energies:")
oechem.OEThrow.Info(" Ligand: %0.2f" % finalEne.GetLigandEnergy())
oechem.OEThrow.Info(" Flexible Protein: %0.2f" % finalEne.GetHostEnergy())
oechem.OEThrow.Info(" Intermolecular: %0.2f" % finalEne.GetInterEnergy())
oechem.OEThrow.Info(" Total: %0.2f" % finalEne.GetTotalEnergy())
oechem.OEWriteDesignUnit(ofs, du)
else:
oechem.OEThrow.Warning("%s: %s" % (du.GetTitle(), oeszybki.OEGetSzybkiError(retCode)))
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Entropy estimation¶
Estimation of solution ligand entropy¶
The following code illustrates how to estimate compound entropy in solution with Szybki TK.
Listing 13: Ligand Entropy
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
szOpts = oeszybki.OELigandEntropyOptions()
opts = oechem.OESimpleAppOptions(szOpts, "LigandEntropy", oechem.OEFileStringType_Mol3D)
if oechem.OEConfigureOpts(opts, argv, False) == oechem.OEOptsConfigureStatus_Help:
return 0
szOpts.UpdateValues(opts)
ifs = oechem.oemolistream()
if not ifs.open(opts.GetInFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetInFile())
for mol in ifs.GetOEMols():
oechem.OEThrow.Info("Title: %s" % mol.GetTitle())
res = oeszybki.OEEntropyResults()
ret_code = oeszybki.OELigandEntropy(res, mol, szOpts)
if ret_code == oeszybki.OESzybkiReturnCode_Success:
oechem.OEThrow.Info(" Configurational Entropy: %0.2f" % res.GetConfigurationalEntropy())
oechem.OEThrow.Info(" Solvation Entropy: %0.2f" % res.GetSolvationEntropy())
oechem.OEThrow.Info(" Total Entropy: %0.2f" % res.GetTotalEntropy())
else:
oechem.OEThrow.Warning("Failed: %s" % oeszybki.OEGetSzybkiError(ret_code))
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Estimation of bound ligand entropy¶
The next example below shows how to calculate entropy of a bound ligand.
Listing 15: Estimation of Bound Ligand Entropy
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(argv=[__name__]):
szOpts = oeszybki.OEBoundEntropyOptions()
opts = oechem.OERefInputAppOptions(szOpts, "BoundEntropy", oechem.OEFileStringType_Mol3D,
oechem.OEFileStringType_DU, "-du")
if oechem.OEConfigureOpts(opts, argv, False) == oechem.OEOptsConfigureStatus_Help:
return 0
szOpts.UpdateValues(opts)
ifs = oechem.oemolistream()
if not ifs.open(opts.GetInFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetInFile())
rfs = oechem.oeifstream()
if not rfs.open(opts.GetRefFile()):
oechem.OEThrow.Fatal("Unable to open %s for reading" % opts.GetRefFile())
du = oechem.OEDesignUnit()
if not oechem.OEReadDesignUnit(rfs, du):
oechem.OEThrow.Fatal("Failed to read design unit")
for mol in ifs.GetOEMols():
oechem.OEThrow.Info("Title: %s" % mol.GetTitle())
res = oeszybki.OEEntropyResults()
ret_code = oeszybki.OEBoundLigandEntropy(res, du, oechem.OEDesignUnitComponents_Protein, mol, szOpts)
if ret_code == oeszybki.OESzybkiReturnCode_Success:
oechem.OEThrow.Info(" Configurational Entropy: %0.2f" % res.GetConfigurationalEntropy())
oechem.OEThrow.Info(" Solvation Entropy: %0.2f" % res.GetSolvationEntropy())
oechem.OEThrow.Info(" Total Entropy: %0.2f" % res.GetTotalEntropy())
else:
oechem.OEThrow.Warning("Failed: %s" % oeszybki.OEGetSzybkiError(ret_code))
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Solvation free energy estimation¶
Listing 16: Solvation Free Energy Estimation
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormSolvOptions()
opts.SetIonicState(oeszybki.OEFreeFormIonicState_Uncharged)
res = oeszybki.OEFreeFormSolvResults()
omol = oechem.OEGraphMol()
if not oeszybki.OEEstimateSolvFreeEnergy(res, omol, mol, opts):
oechem.OEThrow.Error("Failed to calculate solvation free energy for molecule %s" %
mol.GetTitle())
solvenergy = res.GetSolvationFreeEnergy()
oechem.OEThrow.Info("Solvation free energy for compound %s is %6.2f kcal/mol" %
(mol.GetTitle(), solvenergy))
oechem.OEWriteMolecule(ofs, omol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Conformations free energy estimation¶
Warning
This capability should not be used on 32-bit platforms because the memory requirements are too high.
Simple free energy estimation¶
The following code illustrates how to use the high level commands from OEFreeFormConf to estimate conformer free energies in solution with Szybki TK.
Listing 17: Simple Free Energy Estimation
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormConfOptions()
ffconf = oeszybki.OEFreeFormConf(opts)
omol = oechem.OEMol(mol)
if not (ffconf.EstimateFreeEnergies(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Failed to estimate conformational free energies")
res = oeszybki.OEFreeFormConfResults(omol)
oechem.OEThrow.Info("Number of unique conformations: %d" % res.GetNumUniqueConfs())
oechem.OEThrow.Info("Conf. Delta_G Vibrational_Entropy")
oechem.OEThrow.Info(" [kcal/mol] [J/(mol K)]")
for r in res.GetResultsForConformations():
oechem.OEThrow.Info("%2d %10.2f %14.2f" % (r.GetConfIdx(), r.GetDeltaG(),
r.GetVibrationalEntropy()))
oechem.OEWriteMolecule(ofs, omol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Simple restriction energy estimation¶
The following code illustrates how to use the high level commands from OEFreeFormConf to estimate restriction energies on conformers, along with conformer free energies in solution, with Szybki TK.
Listing 18: Simple Restriction Energy Estimation
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormConfOptions()
ffconf = oeszybki.OEFreeFormConf(opts)
omol = oechem.OEMol(mol)
rmol = oechem.OEMol(mol)
if not (ffconf.EstimateFreeEnergies(omol, rmol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Failed to estimate conformational free energies")
res = oeszybki.OEFreeFormConfResults(omol)
oechem.OEThrow.Info("Number of unique conformations: %d" % res.GetNumUniqueConfs())
oechem.OEThrow.Info("Conf. Delta_G Vibrational_Entropy")
oechem.OEThrow.Info(" [kcal/mol] [J/(mol K)]")
for r in res.GetResultsForConformations():
oechem.OEThrow.Info("%2d %10.2f %14.2f" % (r.GetConfIdx(), r.GetDeltaG(),
r.GetVibrationalEntropy()))
rstrRes = oeszybki.OERestrictionEnergyResult(rmol)
oechem.OEThrow.Info("Global strain: %d" % rstrRes.GetGlobalStrain())
oechem.OEThrow.Info("Local strain: %d" % rstrRes.GetLocalStrain())
oechem.OEWriteMolecule(ofs, omol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Advanced free energy estimation¶
The following code illustrates how to use the low level commands from OEFreeFormConfAdvanced to estimate the conformer free energies in solution with Szybki TK. These low level methods of estimation gives an advantage over the high level methods of OEFreeFormConf in that these gives the user control over better managing certain expensive parts of the calculation.
Listing 19: Advanced Free Energy Estimation
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormConfOptions()
ffconf = oeszybki.OEFreeFormConfAdvanced(opts)
# Make a copy of our MCMol. We will execute the FreeFormConf commands on
# the copied molecule so that our original molecule stays intact.
omol = oechem.OEMol(mol)
# Prepare a comprehensive ensemble of molecule conformers. This will
# generate a comprehensive set of conformers, assign solvent charges on the molecule
# and check that the ensemble is otherwise ready for FreeFormConf calculations.
if not (ffconf.PrepareEnsemble(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Failed to prepare ensemble for FreeFormConf calculations")
# Perform loose optimization of the ensemble conformers. We will remove
# duplicates based on the loose optimization, to reduce the time needed for
# tighter, more stricter optimization
if not (ffconf.PreOptimizeEnsemble(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Pre-optimization of the ensembles failed")
# Remove duplicates from the pre-optimized ensemble
if not (ffconf.RemoveDuplicates(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Duplicate removal from the ensembles failed")
# Perform the desired optimization. This uses a stricter convergence
# criteria in the default settings.
if not (ffconf.Optimize(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Optimization of the ensembles failed")
# Remove duplicates to obtain the set of minimum energy conformers
if not (ffconf.RemoveDuplicates(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Duplicate removal from the ensembles failed")
# Perform FreeFormConf free energy calculations. When all the above steps
# have already been performed on the ensemble, this energy calculation
# step is fast.
if not (ffconf.EstimateEnergies(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Estimation of FreeFormConf energies failed")
# Gather results of calculation into a results object for ease of viewing, etc.
res = oeszybki.OEFreeFormConfResults(omol)
oechem.OEThrow.Info("Number of unique conformations: %d" % res.GetNumUniqueConfs())
oechem.OEThrow.Info("Conf. Delta_G Vibrational_Entropy")
oechem.OEThrow.Info(" [kcal/mol] [J/(mol K)]")
for r in res.GetResultsForConformations():
oechem.OEThrow.Info("%2d %10.2f %14.2f" % (r.GetConfIdx(), r.GetDeltaG(),
r.GetVibrationalEntropy()))
oechem.OEWriteMolecule(ofs, omol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Advanced restriction energy estimation¶
The following code illustrates how to use the low level commands from OEFreeFormConfAdvanced to estimate the restriction energies of conformers, along with conformer free energies in solution, with Szybki TK. These low level methods of estimation gives an advantage over the high level methods of OEFreeFormConf in that these gives the user control over better managing certain expensive parts of the calculation.
Listing 20: Advanced Restriction Energy Estimation
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormConfOptions()
ffconf = oeszybki.OEFreeFormConfAdvanced(opts)
# Make a copy of our MCMol. We will execute the FreeFormConf commands on
# the copied molecule so that our original molecule stays intact.
omol = oechem.OEMol(mol)
# Make further copies of our original molecule. The copied molecule(s) would be used
# as source on which retriction energies would be calculated
rmol = oechem.OEMol(mol)
fmol = oechem.OEMol(mol)
# Prepare a comprehensive ensemble of molecule conformers. For calculation
# of restriction energies we want to make sure that all the corresponding free
# conformers are also part of the comprehensive ensemble. This will also
# assign solvent charges on the molecule and check that the ensemble is
# otherwise ready for FreeFormConf calculations. The resulting `fmol`
# contains the correspondig free conformers.
if not (ffconf.PrepareEnsemble(omol, rmol, fmol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Failed to prepare ensemble for FreeFormConf calculations")
# Perform loose optimization of the ensemble conformers. We will remove
# duplicates based on the loose optimization, to reduce the time needed for
# tighter, more stricter optimization
if not (ffconf.PreOptimizeEnsemble(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Pre-optimization of the ensembles failed")
# Remove duplicates from the pre-optimized ensemble
if not (ffconf.RemoveDuplicates(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Duplicate removal from the ensembles failed")
# Perform the desired optimization. This uses a stricter convergence
# criteria in the default settings.
if not (ffconf.Optimize(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Optimization of the ensembles failed")
# Remove duplicates to obtain the set of minimum energy conformers
if not (ffconf.RemoveDuplicates(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Duplicate removal from the ensembles failed")
# Perform FreeFormConf free energy calculations. When all the above steps
# have already been performed on the ensemble, this energy calculation
# step is fast.
if not (ffconf.EstimateEnergies(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Estimation of FreeFormConf energies failed")
# Gather results of calculation into a results object for ease of viewing, etc.
res = oeszybki.OEFreeFormConfResults(omol)
oechem.OEThrow.Info("Number of unique conformations: %d" % res.GetNumUniqueConfs())
oechem.OEThrow.Info("Conf. Delta_G Vibrational_Entropy")
oechem.OEThrow.Info(" [kcal/mol] [J/(mol K)]")
for r in res.GetResultsForConformations():
oechem.OEThrow.Info("%2d %10.2f %14.2f" % (r.GetConfIdx(), r.GetDeltaG(),
r.GetVibrationalEntropy()))
# Identify the corresponding conformer(s) to the free minimized conformer(s).
# If identified, the corresponding (Conf)Free energy information is also
# copied to the free conformers
if not (ffconf.IdentifyConformer(fmol, omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Identification of free conformer(s) failed")
# Estimate restriction energies. Since both restricted and free conformer
# energy components are already available, this operation is fast.
if not (ffconf.EstimateRestrictionEnergy(fmol, rmol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Restriction energy estimation failed")
# Gather restriction energies into a results object for ease of viewing, etc.
rstrRes = oeszybki.OERestrictionEnergyResult(fmol)
oechem.OEThrow.Info("Global strain: %f" % rstrRes.GetGlobalStrain())
oechem.OEThrow.Info("Local strain: %f" % rstrRes.GetLocalStrain())
# Optionally it is desired to perform a restrained optimization of the
# restricted conformer(s) to brush out any energy differences due to
# force field constaints or the sources of coonformer coordinates. Note: The
# high level EstimateFreeEnergy method does not perform this opertion.
if not (ffconf.OptimizeRestraint(rmol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Restraint optimization of the conformer(s) failed")
# Estimate restriction energies on this optimized conformers.
# Since both restricted and free conformer energy components
# are already available, this operation is fast.
if not (ffconf.EstimateRestrictionEnergy(fmol, rmol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Restriction energy estimation failed")
# Gather restriction energies into a results object for ease of viewing, etc.
rstrRes = oeszybki.OERestrictionEnergyResult(fmol)
oechem.OEThrow.Info("Global strain: %f" % rstrRes.GetGlobalStrain())
oechem.OEThrow.Info("Local strain: %f" % rstrRes.GetLocalStrain())
oechem.OEWriteMolecule(ofs, omol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Finding similar conformers¶
The following code illustrates how to find similar conformers to the ones at hand, from a pool of minimum energy conformers.
Listing 21: Finding Similar Conformers
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
def main(args):
if len(args) != 3:
oechem.OEThrow.Usage("%s <input> <output>" % 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.OEFreeFormConfOptions()
ffconf = oeszybki.OEFreeFormConf(opts)
# Estimate free energies to ontain the minimum energy conformers
omol = oechem.OEMol(mol)
if not (ffconf.EstimateFreeEnergies(omol) == oeszybki.OEFreeFormReturnCode_Success):
oechem.OEThrow.Error("Failed to estimate conformational free energies")
# Find similar conformers to the ones we started with, from the
# pool of minimum energy conformers
fmol = oechem.OEMol(mol)
for conf in mol.GetConfs():
ffconf.FindSimilarConfs(fmol, omol, conf, oechem.OESimilarByRMSD(0.05))
oechem.OEWriteMolecule(ofs, fmol)
return 0
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code
Torsion scan¶
The following code shows how to scan all torsions in the input molecule
Listing 22: Perform torsion scan for all torsions in the input molecule
#!/usr/bin/env python
# (C) 2022 Cadence Design Systems, Inc. (Cadence)
# All rights reserved.
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of Cadence products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. Cadence claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable Cadence offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED. OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall Cadence be
# liable for any damages or liability in connection with the Sample Code
# or its use.
import sys
from openeye import oechem
from openeye import oeszybki
###############################################################
# USED TO GENERATE CODE SNIPPETS FOR THE SZYBKI DOCUMENTATION
###############################################################
def main(argv=sys.argv):
if len(argv) != 2:
oechem.OEThrow.Usage("%s <infile>" % argv[0])
ifs = oechem.oemolistream()
if not ifs.open(argv[1]):
oechem.OEThrow.Fatal("Unable to open %s for reading" % argv[1])
mol = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol)
outmol = oechem.OEMol()
opts = oeszybki.OETorsionScanOptions()
opts.SetDelta(30.0)
opts.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94)
opts.SetSolvationType(oeszybki.OESolventModel_NoSolv)
for tor in oechem.OEGetTorsions(mol):
print("Torsion: %d %d %d %d" %
(tor.a.GetIdx(), tor.b.GetIdx(), tor.c.GetIdx(), tor.d.GetIdx()))
for res in oeszybki.OETorsionScan(outmol, mol, tor, opts):
print("%.2f %.2f" % (res.GetAngle(), res.GetEnergy()))
if __name__ == "__main__":
sys.exit(main(sys.argv))
Download code