def SplitMolComplexAllSites(oms, inmol, splitCovalent):
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if splitCovalent:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ALL-SITES-SPLIT>
opt = oechem.OESplitMolComplexOptions()
allSites = 0
opt.ResetFilters(allSites)
opt.SetSplitCovalent()
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ALL-SITES-SPLIT>
if oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
WriteResultMols(oms, lig, prot, wat, other)
else:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ALL-SITES>
opt = oechem.OESplitMolComplexOptions()
allSites = 0
opt.ResetFilters(allSites)
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ALL-SITES>
if oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
WriteResultMols(oms, lig, prot, wat, other)
def SplitMolComplex(oms, inmol, splitCovalent, separateResidues):
# limiting lig, prot and wat to just near the first binding site
# (a very common pattern)
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if not splitCovalent and not separateResidues:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-SIMPLE>
# for input molecule inmol ...
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if oechem.OESplitMolComplex(lig, prot, wat, other, inmol):
# work with the output molecules lig, prot, ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-SIMPLE>
WriteResultMols(oms, lig, prot, wat, other)
elif splitCovalent and not separateResidues:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-SPLIT-COVALENT>
# given input and output molecules ...
opt = oechem.OESplitMolComplexOptions()
opt.SetSplitCovalent()
if oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
# ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-SPLIT-COVALENT>
WriteResultMols(oms, lig, prot, wat, other)
elif not splitCovalent and separateResidues:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-SEPARATE-RES>
opt = oechem.OESplitMolComplexOptions()
opt.SetSeparateResidues()
if not oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
oechem.OEThrow.Fatal("Unable to split mol complex from %s" %
inmol.GetTitle())
# @ </SNIPPET-SPLIT-MOL-COMPLEX-SEPARATE-RES>
else:
WriteResultMols(oms, lig, prot, wat, other)
else:
# @ <SNIPPET-SPLIT-MOL-COMPLEX-OPTIONS>
opt = oechem.OESplitMolComplexOptions()
opt.SetSplitCovalent(splitCovalent)
opt.SetSeparateResidues(separateResidues)
if not oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
oechem.OEThrow.Fatal("Unable to split mol complex from %s" %
inmol.GetTitle())
# @ </SNIPPET-SPLIT-MOL-COMPLEX-OPTIONS>
else:
WriteResultMols(oms, lig, prot, wat, other)
def split_complex_from_system(self):
with self.logger("split_complex_from_system") as logger:
if self.input_pdb is not None:
pdb = oechem.OEMol()
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
ifs = oechem.oemolistream()
ifs.SetFlavor(oechem.OEFormat_PDB, oechem.OEIFlavor_PDB_Default
| oechem.OEIFlavor_PDB_DATA
| oechem.OEIFlavor_PDB_ALTLOC) # noqa
if ifs.open(self.input_pdb):
oechem.OEReadMolecule(ifs, pdb)
else:
logger.error("Could not open file!")
ifs.close()
logger.log(f"Reading input PDB {self.input_pdb}")
if not oechem.OESplitMolComplex(lig, prot, wat, other, pdb):
logger.failure("could not split complex. exiting",
exit_all=True)
else:
logger.log(
f"Split complex. atom sizes-- lig: {len(list(lig.GetAtoms()))}, prot: {len(list(prot.GetAtoms()))}, water: {len(list(wat.GetAtoms()))}, other: {len(list(other.GetAtoms()))}"
)
else:
pdb = oechem.OEMol()
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
ifs = oechem.oemolistream()
ifs.SetFlavor(oechem.OEFormat_PDB, oechem.OEIFlavor_PDB_Default
| oechem.OEIFlavor_PDB_DATA
| oechem.OEIFlavor_PDB_ALTLOC) # noqa
if ifs.open(self.input_pdb):
oechem.OEReadMolecule(ifs, pdb)
else:
logger.error("Could not open file!")
ifs.close()
logger.log(f"Reading input PDB {self.input_pdb}")
if not oechem.OESplitMolComplex(lig, prot, wat, other, pdb):
logger.failure("could not split complex. exiting",
exit_all=True)
else:
logger.log(
f"Split complex. atom sizes-- lig: {len(list(lig.GetAtoms()))}, prot: {len(list(prot.GetAtoms()))}, water: {len(list(wat.GetAtoms()))}, other: {len(list(other.GetAtoms()))}"
)
ifs = oechem.oemolistream(self.lig)
lig = oechem.OEMol()
oechem.OEReadMolecule(ifs, lig)
ifs.close()
return prot, lig
def choose_action(self, pdb_string):
with self.logger("choose_action") as logger:
with tempfile.TemporaryDirectory() as dirname:
with open("{}/test.pdb".format(dirname), 'w') as f:
f.write(pdb_string)
pdb = oechem.OEMol()
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
ifs = oechem.oemolistream()
ifs.SetFlavor(oechem.OEFormat_PDB, oechem.OEIFlavor_PDB_Default
| oechem.OEIFlavor_PDB_DATA
| oechem.OEIFlavor_PDB_ALTLOC) # noqa
if not ifs.open("{}/test.pdb".format(dirname)):
logger.log("crap")
oechem.OEReadMolecule(ifs, pdb)
ifs.close()
if not oechem.OESplitMolComplex(lig, prot, wat, other, pdb):
logger.failure("could not split complex. exiting",
exit_all=True)
else:
logger.log("atom sizes for incoming step",
len(list(lig.GetAtoms())),
len(list(prot.GetAtoms())),
len(list(wat.GetAtoms())),
len(list(other.GetAtoms())))
original_smiles, oeclean_smiles = self.env.action.get_new_action_set(
aligner=lig)
data = self.getscores(
original_smiles,
oeclean_smiles,
prot,
lig,
num_returns=self.num_returns,
return_docked_pose=self.return_docked_pose)
not_worked = True
idxs = list(range(len(data)))
idx = idxs.pop(0)
while not_worked:
try:
new_mol, new_mol2, gs, action = data[idx]
self.env.systemloader.reload_system(
gs, new_mol, "{}/test.pdb".format(dirname))
self.env.openmm_simulation = self.env.config.openmmWrapper.get_obj(
self.env.systemloader, self.env.openmm_simulation)
not_worked = False
except Exception as e:
logger.error("Could not buid system for smiles", gs,
"with exception", e)
traceback.print_tb(e.__traceback__)
if len(idxs) == 0:
logger.failure("No system could build",
exit_all=True)
idx = idxs.pop(0)
self.env.action.apply_action(new_mol2, action)
return new_mol2, action
def split(self):
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if oechem.OESplitMolComplex(lig, prot, wat, other, self.inmol):
# work with the output molecules lig, prot, ...
return [prot, lig]
else:
raise Exception('failure to detect prot & lig')
def split(mol):
"""
This function splits the passed system in protein, ligand,
water and excipients
Parameters:
----------
mol : oechem.OEMol
The bio-molecular system to split
Output:
-------
protein : oechem.OEMol
The split protein
ligand : oechem.OEMol
The split ligand
wat : oechem.OEMol
The spit water
other : oechem.OEMol
The excipients
"""
# Set empty molecule containers
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEMol()
other = oechem.OEMol()
# Define the Filter options before the splitting
opt = oechem.OESplitMolComplexOptions()
# The protein filter is set to avoid that multiple
# chains are separated during the splitting
pf = oechem.OEMolComplexFilterFactory(oechem.OEMolComplexFilterCategory_Protein)
# The ligand filter is set to recognize just the ligand
lf = oechem.OEMolComplexFilterFactory(oechem.OEMolComplexFilterCategory_Ligand)
# The water filter is set to recognize just water molecules
wf = oechem.OEMolComplexFilterFactory(oechem.OEMolComplexFilterCategory_Water)
opt.SetProteinFilter(pf)
opt.SetLigandFilter(lf)
opt.SetWaterFilter(wf)
# Splitting the system
if not oechem.OESplitMolComplex(lig, prot, wat, other, mol, opt):
oechem.OEThrow.Fatal('Unable to split the complex')
# At this point prot contains the protein, lig contains the ligand,
# wat contains the water and excipients contains the excipients
return prot, lig, wat, other
def split_complex(protein, ligand, sopts, complexmol):
water = oechem.OEGraphMol()
other = oechem.OEGraphMol()
pfilter = sopts.GetProteinFilter()
wfilter = sopts.GetWaterFilter()
sopts.SetProteinFilter(oechem.OEOrRoleSet(pfilter, wfilter))
filter = oechem.OEMolComplexFilterCategory_Nothing
sopts.SetWaterFilter(oechem.OEMolComplexFilterFactory(filter))
oechem.OESplitMolComplex(ligand, protein, water, other, complexmol, sopts)
return ligand.NumAtoms() != 0 and protein.NumAtoms() != 0
def SplitMolComplexCombineFilters(oms, inmol):
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
# @ <SNIPPET-SPLIT-MOL-COMPLEX-COMBINE-FILTERS>
opt = oechem.OESplitMolComplexOptions()
p = opt.GetProteinFilter()
w = opt.GetWaterFilter()
opt.SetProteinFilter(oechem.OEOrRoleSet(p, w))
opt.SetWaterFilter(
oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Nothing))
# @ </SNIPPET-SPLIT-MOL-COMPLEX-COMBINE-FILTERS>
if oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opt):
WriteResultMols(oms, lig, prot, wat, other)
def main(argv=[__name__]):
itf = oechem.OEInterface()
oechem.OEConfigure(itf, InterfaceData)
oedepict.OEConfigureImageWidth(itf, 900.0)
oedepict.OEConfigureImageHeight(itf, 600.0)
oedepict.OEConfigure2DMolDisplayOptions(
itf, oedepict.OE2DMolDisplaySetup_AromaticStyle)
oechem.OEConfigureSplitMolComplexOptions(
itf, oechem.OESplitMolComplexSetup_LigName)
if not oechem.OEParseCommandLine(itf, argv):
return 1
iname = itf.GetString("-complex")
oname = itf.GetString("-out")
ifs = oechem.oemolistream()
if not ifs.open(iname):
oechem.OEThrow.Fatal("Cannot open input file!")
ext = oechem.OEGetFileExtension(oname)
if not oedepict.OEIsRegisteredImageFile(ext):
oechem.OEThrow.Fatal("Unknown image type!")
ofs = oechem.oeofstream()
if not ofs.open(oname):
oechem.OEThrow.Fatal("Cannot open output file!")
complexmol = oechem.OEGraphMol()
if not oechem.OEReadMolecule(ifs, complexmol):
oechem.OEThrow.Fatal("Unable to read molecule from %s" % iname)
if not oechem.OEHasResidues(complexmol):
oechem.OEPerceiveResidues(complexmol, oechem.OEPreserveResInfo_All)
# Separate ligand and protein
sopts = oechem.OESplitMolComplexOptions()
oechem.OESetupSplitMolComplexOptions(sopts, itf)
ligand = oechem.OEGraphMol()
protein = oechem.OEGraphMol()
water = oechem.OEGraphMol()
other = oechem.OEGraphMol()
pfilter = sopts.GetProteinFilter()
wfilter = sopts.GetWaterFilter()
sopts.SetProteinFilter(oechem.OEOrRoleSet(pfilter, wfilter))
sopts.SetWaterFilter(
oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Nothing))
oechem.OESplitMolComplex(ligand, protein, water, other, complexmol, sopts)
if ligand.NumAtoms() == 0:
oechem.OEThrow.Fatal("Cannot separate complex!")
# Perceive interactions
asite = oechem.OEInteractionHintContainer(protein, ligand)
if not asite.IsValid():
oechem.OEThrow.Fatal("Cannot initialize active site!")
asite.SetTitle(ligand.GetTitle())
oechem.OEPerceiveInteractionHints(asite)
oegrapheme.OEPrepareActiveSiteDepiction(asite)
# Depict active site with interactions
width, height = oedepict.OEGetImageWidth(itf), oedepict.OEGetImageHeight(
itf)
image = oedepict.OEImage(width, height)
cframe = oedepict.OEImageFrame(image, width * 0.80, height,
oedepict.OE2DPoint(0.0, 0.0))
lframe = oedepict.OEImageFrame(image, width * 0.20, height,
oedepict.OE2DPoint(width * 0.80, 0.0))
opts = oegrapheme.OE2DActiveSiteDisplayOptions(cframe.GetWidth(),
cframe.GetHeight())
oedepict.OESetup2DMolDisplayOptions(opts, itf)
adisp = oegrapheme.OE2DActiveSiteDisplay(asite, opts)
oegrapheme.OERenderActiveSite(cframe, adisp)
lopts = oegrapheme.OE2DActiveSiteLegendDisplayOptions(10, 1)
oegrapheme.OEDrawActiveSiteLegend(lframe, adisp, lopts)
oedepict.OEWriteImage(oname, image)
return 0
def main(argv=[__name__]):
itf = oechem.OEInterface()
oechem.OEConfigure(itf, InterfaceData)
oedepict.OEConfigureImageWidth(itf, 600.0)
oedepict.OEConfigureImageHeight(itf, 600.0)
oedepict.OEConfigure2DMolDisplayOptions(itf, oedepict.OE2DMolDisplaySetup_AromaticStyle)
oechem.OEConfigureSplitMolComplexOptions(itf, oechem.OESplitMolComplexSetup_LigName)
if not oechem.OEParseCommandLine(itf, argv):
return 1
iname = itf.GetString("-complex")
oname = itf.GetString("-out")
ifs = oechem.oemolistream()
if not ifs.open(iname):
oechem.OEThrow.Fatal("Cannot open input file!")
ext = oechem.OEGetFileExtension(oname)
if not oedepict.OEIsRegisteredImageFile(ext):
oechem.OEThrow.Fatal("Unknown image type!")
ofs = oechem.oeofstream()
if not ofs.open(oname):
oechem.OEThrow.Fatal("Cannot open output file!")
complexmol = oechem.OEGraphMol()
if not oechem.OEReadMolecule(ifs, complexmol):
oechem.OEThrow.Fatal("Unable to read molecule from %s" % iname)
if not oechem.OEHasResidues(complexmol):
oechem.OEPerceiveResidues(complexmol, oechem.OEPreserveResInfo_All)
# Separate ligand and protein
sopts = oechem.OESplitMolComplexOptions()
oechem.OESetupSplitMolComplexOptions(sopts, itf)
ligand = oechem.OEGraphMol()
protein = oechem.OEGraphMol()
water = oechem.OEGraphMol()
other = oechem.OEGraphMol()
oechem.OESplitMolComplex(ligand, protein, water, other, complexmol, sopts)
if ligand.NumAtoms() == 0:
oechem.OEThrow.Fatal("Cannot separate complex!")
# Calculate average BFactor of the whole complex
avgbfactor = GetAverageBFactor(complexmol)
# Calculate minimum and maximum BFactor of the ligand and its environment
minbfactor, maxbfactor = GetMinAndMaxBFactor(ligand, protein)
# Attach to each ligand atom the average BFactor of the nearby protein atoms
stag = "avg residue BFfactor"
itag = oechem.OEGetTag(stag)
SetAverageBFactorOfNearbyProteinAtoms(ligand, protein, itag)
oechem.OEThrow.Info("Average BFactor of the complex = %+.3f" % avgbfactor)
oechem.OEThrow.Info("Minimum BFactor of the ligand and its environment = %+.3f" % minbfactor)
oechem.OEThrow.Info("Maximum BFactor of the ligand and its environment = %+.3f" % maxbfactor)
# Create image
imagewidth, imageheight = oedepict.OEGetImageWidth(itf), oedepict.OEGetImageHeight(itf)
image = oedepict.OEImage(imagewidth, imageheight)
mframe = oedepict.OEImageFrame(image, imagewidth,
imageheight * 0.90, oedepict.OE2DPoint(0.0, 0.0))
lframe = oedepict.OEImageFrame(image, imagewidth, imageheight * 0.10,
oedepict.OE2DPoint(0.0, imageheight * 0.90))
opts = oedepict.OE2DMolDisplayOptions(mframe.GetWidth(), mframe.GetHeight(),
oedepict.OEScale_AutoScale)
oedepict.OESetup2DMolDisplayOptions(opts, itf)
opts.SetAtomColorStyle(oedepict.OEAtomColorStyle_WhiteMonochrome)
# Create BFactor color gradient
colorg = oechem.OELinearColorGradient()
colorg.AddStop(oechem.OEColorStop(0.0, oechem.OEDarkBlue))
colorg.AddStop(oechem.OEColorStop(10.0, oechem.OELightBlue))
colorg.AddStop(oechem.OEColorStop(25.0, oechem.OEYellowTint))
colorg.AddStop(oechem.OEColorStop(50.0, oechem.OERed))
colorg.AddStop(oechem.OEColorStop(100.0, oechem.OEDarkRose))
# Prepare ligand for depiction
oegrapheme.OEPrepareDepictionFrom3D(ligand)
arcfxn = BFactorArcFxn(colorg, itag)
for atom in ligand.GetAtoms():
oegrapheme.OESetSurfaceArcFxn(ligand, atom, arcfxn)
opts.SetScale(oegrapheme.OEGetMoleculeSurfaceScale(ligand, opts))
# Render ligand and visualize BFactor
disp = oedepict.OE2DMolDisplay(ligand, opts)
colorbfactor = ColorLigandAtomByBFactor(colorg)
oegrapheme.OEAddGlyph(disp, colorbfactor, oechem.OEIsTrueAtom())
oegrapheme.OEDraw2DSurface(disp)
oedepict.OERenderMolecule(mframe, disp)
# Draw color gradient
opts = oegrapheme.OEColorGradientDisplayOptions()
opts.SetColorStopPrecision(1)
opts.AddMarkedValue(avgbfactor)
opts.SetBoxRange(minbfactor, maxbfactor)
oegrapheme.OEDrawColorGradient(lframe, colorg, opts)
oedepict.OEWriteImage(oname, image)
return 0
def __init__(self,
env,
sort='dscores',
return_docked_pose=False,
num_returns=-1,
orig_pdb=None,
useHybrid=False,
trackHScores=True,
optimize=False):
self.logger = make_message_writer(env.verbose, self.__class__.__name__)
with self.logger("__init__") as logger:
self.sort = sort
if self.sort not in ['iscores', 'dscores', 'hscores', 'pscores']:
logger.failure(
f"{self.sort} is not a valid sorting method. Exiting",
exit_all=True)
self.return_docked_pose = return_docked_pose
self.num_returns = num_returns
self.env = env
self.orig_pdb = orig_pdb
self.start_dobj = None
self.start_receptor = None
self.track_hscores = trackHScores
if not self.track_hscores and self.sort == 'hscores':
logger.error(
"Track hscores is set to false but the sorting method desired is hscores. Assuming this was error, continuing by setting track_hscores to True"
)
self.track_hscores = True
self.past_receptors = []
self.past_dockobjs = []
self.past_coordinates = []
self.optimize = optimize
self.dockmethod = oedocking.OEDockMethod_Hybrid if useHybrid else oedocking.OEDockMethod_Chemgauss4
if (not (self.sort != 'iscores'
and self.optimize)) and self.orig_pdb is not None:
pdb = oechem.OEMol()
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
ifs = oechem.oemolistream(self.orig_pdb)
oechem.OEReadMolecule(ifs, pdb)
ifs.close()
if not oechem.OESplitMolComplex(lig, prot, wat, other, pdb):
logger.failure("Could not split complex", exit_all=True)
self.start_receptor = oechem.OEGraphMol()
logger.log("Building initial receptor file...")
oedocking.OEMakeReceptor(self.start_receptor, prot, lig)
self.start_dobj = oedocking.OEDock(self.dockmethod)
self.start_dobj.Initialize(self.start_receptor)
assert (self.start_dobj.IsInitialized())
logger.log("done")
elif self.sort != 'iscores' and self.optimize:
logger.log(
"Skipping building inital receptor because optmize is set and sorting method is not iscore"
)
else:
logger.log(
"Skipping building inital receptor because orig_pdb was not provided."
)
def main(argv=[__name__]):
itf = oechem.OEInterface()
oechem.OEConfigure(itf, InterfaceData)
oechem.OEConfigureSplitMolComplexOptions(
itf, oechem.OESplitMolComplexSetup_LigName)
if not oechem.OEParseCommandLine(itf, argv):
return 1
iname = itf.GetString("-complex")
ifs = oechem.oemolistream()
if not ifs.open(iname):
oechem.OEThrow.Fatal("Unable to open %s for reading" % iname)
complexmol = oechem.OEGraphMol()
if not oechem.OEReadMolecule(ifs, complexmol):
oechem.OEThrow.Fatal("Unable to read molecule from %s" % iname)
if not oechem.OEHasResidues(complexmol):
oechem.OEPerceiveResidues(complexmol, oechem.OEPreserveResInfo_All)
# Separate ligand and protein
sopts = oechem.OESplitMolComplexOptions()
oechem.OESetupSplitMolComplexOptions(sopts, itf)
ligand = oechem.OEGraphMol()
protein = oechem.OEGraphMol()
water = oechem.OEGraphMol()
other = oechem.OEGraphMol()
pfilter = sopts.GetProteinFilter()
wfilter = sopts.GetWaterFilter()
sopts.SetProteinFilter(oechem.OEOrRoleSet(pfilter, wfilter))
sopts.SetWaterFilter(
oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Nothing))
oechem.OESplitMolComplex(ligand, protein, water, other, complexmol, sopts)
if ligand.NumAtoms() == 0:
oechem.OEThrow.Fatal("Cannot separate complex!")
# Perceive interactions
asite = oechem.OEInteractionHintContainer(protein, ligand)
if not oechem.OEIsValidActiveSite(asite):
oechem.OEThrow.Fatal("Cannot initialize active site!")
oechem.OEPerceiveInteractionHints(asite)
print("Number of interactions:", asite.NumInteractions())
for itype in oechem.OEGetActiveSiteInteractionHintTypes():
numinters = asite.NumInteractions(
oechem.OEHasInteractionHintType(itype))
if numinters == 0:
continue
print("%d %s :" % (numinters, itype.GetName()))
inters = [
s for s in asite.GetInteractions(
oechem.OEHasInteractionHintType(itype))
]
print("\n".join(sorted(GetInteractionString(s) for s in inters)))
print("\nResidue interactions:")
for res in oechem.OEGetResidues(
asite.GetMolecule(oechem.OEProteinInteractionHintComponent())):
PrintResidueInteractions(asite, res)
print("\nLigand atom interactions:")
for atom in asite.GetMolecule(
oechem.OELigandInteractionHintComponent()).GetAtoms():
PrintLigandAtomInteractions(asite, atom)
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)
def split(complex, ligand_res_name='LIG'):
"""
This function splits the passed system in protein, ligand,
water and excipients
Parameters:
----------
complex : oechem.OEMol
The bio-molecular complex to split
ligand_res_name : Python string
The ligand residue name used to recognize the ligand
Output:
-------
protein : oechem.OEMol
The split protein
ligand : oechem.OEMol
The split ligand
wat : oechem.OEMol
The spit water
other : oechem.OEMol
The excipients
"""
# Set empty molecule containers
prot = oechem.OEMol()
lig = oechem.OEMol()
wat = oechem.OEMol()
other = oechem.OEMol()
# Define the Filter options before the splitting
opt = oechem.OESplitMolComplexOptions()
# The protein filter is set to avoid that multiple
# chains are separated during the splitting and peptide
# molecules are recognized as ligands
pf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Protein)
peptide = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Peptide)
protein_filter = oechem.OEOrRoleSet(pf, peptide)
opt.SetProteinFilter(protein_filter)
# The ligand filter is set to recognize just the ligand
lf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Ligand)
not_protein_filter = oechem.OENotRoleSet(protein_filter)
ligand_filter = oechem.OEAndRoleSet(lf, not_protein_filter)
opt.SetLigandFilter(ligand_filter)
# The water filter is set to recognize just water molecules
wf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Water)
opt.SetWaterFilter(wf)
# Set Category
cat = oechem.OEMolComplexCategorizer()
cat.AddLigandName(ligand_res_name)
opt.SetCategorizer(cat)
# Splitting the system
if not oechem.OESplitMolComplex(lig, prot, wat, other, complex, opt):
raise ValueError('Unable to split the complex')
# At this point prot contains the protein, lig contains the ligand,
# wat contains the water and excipients contains the excipients
return prot, lig, wat, other
def split(complex, ligand_res_name='LIG'):
"""
This function splits the passed system in protein, ligand,
water and excipients.
Parameters:
----------
complex : oechem.OEMol
The bio-molecular complex to split
ligand_res_name : Python string
The ligand residue name used to recognize the ligand
Output:
-------
protein : oechem.OEMol
The split protein
ligand : oechem.OEMol
The split ligand
wat : oechem.OEMol
The spit water
cofactors : oechem.OEMol
The cofactors
lipids : oechem.OEMol
The lipids
metals : oechem.OEMol
The metals
excipients : oechem.OEMol
The excipients
"""
# Set empty molecule containers
protein = oechem.OEMol()
ligand = oechem.OEMol()
water = oechem.OEMol()
other = oechem.OEMol()
# Define the Filter options before the splitting
opt = oechem.OESplitMolComplexOptions()
# The protein filter is set to avoid that multiple
# chains are separated during the splitting and peptide
# molecules are recognized as ligands
pf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Protein)
peptide = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Peptide)
protein_filter = oechem.OEOrRoleSet(pf, peptide)
opt.SetProteinFilter(protein_filter)
# The ligand filter is set to recognize just the ligand
lf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Ligand)
not_protein_filter = oechem.OENotRoleSet(protein_filter)
ligand_filter = oechem.OEAndRoleSet(lf, not_protein_filter)
opt.SetLigandFilter(ligand_filter)
# The water filter is set to recognize just water molecules
wf = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Water)
opt.SetWaterFilter(wf)
# Set Category
cat = oechem.OEMolComplexCategorizer()
cat.AddLigandName(ligand_res_name)
opt.SetCategorizer(cat)
# Splitting the system
if not oechem.OESplitMolComplex(ligand, protein, water, other, complex,
opt):
raise ValueError('Unable to split the complex')
cofactors = oechem.OEMol()
lipids = oechem.OEMol()
metals = oechem.OEMol()
excipients = oechem.OEMol()
# Splitting the subsystem
if other.NumAtoms():
opt_other = oechem.OESplitMolComplexOptions()
lipid_filter = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Lipid)
opt_other.SetProteinFilter(lipid_filter)
cofactor_filter = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Cofactor)
opt_other.SetLigandFilter(cofactor_filter)
metal_filter = oechem.OEMolComplexFilterFactory(
oechem.OEMolComplexFilterCategory_Metal)
opt_other.SetWaterFilter(metal_filter)
# Set Category
cat_other = oechem.OEMolComplexCategorizer()
opt_other.SetCategorizer(cat_other)
if not oechem.OESplitMolComplex(cofactors, lipids, metals, excipients,
other, opt_other):
raise ValueError('Unable to split the Subcategories')
return protein, ligand, water, cofactors, lipids, metals, excipients
def main(argv=[__name__]):
itf = oechem.OEInterface(InterfaceData)
oechem.OEConfigureSplitMolComplexOptions(itf)
if not oechem.OEParseCommandLine(itf, argv):
oechem.OEThrow.Fatal("Unable to interpret command line!")
if itf.GetBool("-verbose"):
oechem.OEThrow.SetLevel(oechem.OEErrorLevel_Verbose)
iname = itf.GetString("-in")
oname = itf.GetString("-out")
ims = oechem.oemolistream()
if not itf.GetUnsignedInt("-modelnum") == 1:
ims.SetFlavor(oechem.OEFormat_PDB,
oechem.OEGetDefaultIFlavor(oechem.OEFormat_PDB) & ~oechem.OEIFlavor_PDB_ENDM)
if not ims.open(iname):
oechem.OEThrow.Fatal("Cannot open input file!")
oms = oechem.oemolostream()
if not oms.open(oname):
oechem.OEThrow.Fatal("Cannot open output file!")
inmol = oechem.OEGraphMol()
if not oechem.OEReadMolecule(ims, inmol):
oechem.OEThrow.Fatal("Cannot read input file!")
opts = oechem.OESplitMolComplexOptions()
oechem.OESetupSplitMolComplexOptions(opts, itf)
if itf.GetBool("-verbose"):
# don't bother counting sites unless we're going to print them
numSites = oechem.OECountMolComplexSites(inmol, opts)
oechem.OEThrow.SetLevel(oechem.OEErrorLevel_Verbose)
oechem.OEThrow.Verbose("sites %d" % numSites)
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if not oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opts):
oechem.OEThrow.Fatal("Unable to split mol complex from %s" % iname)
if not lig.NumAtoms() == 0:
oechem.OEThrow.Verbose(" lig %s" % lig.GetTitle())
oechem.OEWriteMolecule(oms, lig)
if not prot.NumAtoms() == 0:
oechem.OEThrow.Verbose(" prot %s" % prot.GetTitle())
oechem.OEWriteMolecule(oms, prot)
if not wat.NumAtoms() == 0:
oechem.OEThrow.Verbose(" wat %s" % wat.GetTitle())
oechem.OEWriteMolecule(oms, wat)
if not other.NumAtoms() == 0:
oechem.OEThrow.Verbose("other %s" % other.GetTitle())
oechem.OEWriteMolecule(oms, other)
oms.close()
def main(argv=[__name__]):
itf = oechem.OEInterface(InterfaceData)
oechem.OEConfigureSplitMolComplexOptions(itf)
if not oechem.OEParseCommandLine(itf, argv):
oechem.OEThrow.Fatal("Unable to interpret command line!")
opts = oechem.OESplitMolComplexOptions()
oechem.OESetupSplitMolComplexOptions(opts, itf)
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ITF>
iname = itf.GetString("-in")
oname = itf.GetString("-out")
ims = oechem.oemolistream()
if not itf.GetUnsignedInt("-modelnum") == 1:
ims.SetFlavor(
oechem.OEFormat_PDB,
oechem.OEGetDefaultIFlavor(oechem.OEFormat_PDB)
& ~oechem.OEIFlavor_PDB_ENDM)
if not ims.open(iname):
oechem.OEThrow.Fatal("Cannot open input file!")
oms = oechem.oemolostream()
if not oms.open(oname):
oechem.OEThrow.Fatal("Cannot open output file!")
bfixTitles = (oms.GetFormat() == oechem.OEFormat_SDF)
sTitleSDTag = "TITLE"
inmol = oechem.OEGraphMol()
if not oechem.OEReadMolecule(ims, inmol):
oechem.OEThrow.Fatal("Cannot read input file!")
lig = oechem.OEGraphMol()
prot = oechem.OEGraphMol()
wat = oechem.OEGraphMol()
other = oechem.OEGraphMol()
if not oechem.OESplitMolComplex(lig, prot, wat, other, inmol, opts):
oechem.OEThrow.Fatal("Unable to split mol complex from %s" % iname)
if not lig.NumAtoms() == 0:
if bfixTitles:
FixSDFTitle(sTitleSDTag, lig)
oechem.OEWriteMolecule(oms, lig)
if not prot.NumAtoms() == 0:
if bfixTitles:
FixSDFTitle(sTitleSDTag, prot)
oechem.OEWriteMolecule(oms, prot)
if not wat.NumAtoms() == 0:
if bfixTitles:
FixSDFTitle(sTitleSDTag, wat)
oechem.OEWriteMolecule(oms, wat)
if not other.NumAtoms() == 0:
if bfixTitles:
FixSDFTitle(sTitleSDTag, other)
oechem.OEWriteMolecule(oms, other)
oms.close()