def _prepare_ligand_template(
self, ligand_template: pd.Series, kinase_domain: oechem.OEGraphMol
) -> oechem.OEGraphMol:
"""
Prepare a PDB structure containing the ligand template of interest.
Parameters
----------
ligand_template: pd.Series
A data series containing entries 'pdb', 'chain', 'ligand' and 'alt'.
kinase_domain: oechem.OEGraphMol
An OpenEye molecule holding the kinase domain the ligand template structure should be superposed to.
Returns
-------
: oechem.OEGraphMol
An OpenEye molecule holding the prepared ligand structure.
"""
from openeye import oechem
from ..modeling.OEModeling import (
read_molecules,
select_chain,
select_altloc,
remove_non_protein,
superpose_proteins,
)
from ..utils import FileDownloader
logging.debug("Interpreting structure ...")
ligand_template_structure = PDBProtein(ligand_template.pdb)
if not ligand_template_structure.path.is_file():
logging.debug(f"Downloading PDB entry {ligand_template.pdb} ...")
FileDownloader.rcsb_structure_pdb(ligand_template.pdb)
logging.debug("Reading structure ...")
ligand_template_structure = read_molecules(ligand_template_structure.path)[0]
logging.debug("Selecting chain ...")
ligand_template_structure = select_chain(ligand_template_structure, ligand_template.chain)
logging.debug("Selecting alternate location ...")
ligand_template_structure = select_altloc(ligand_template_structure, ligand_template.alt)
logging.debug("Removing everything but protein, water and ligand of interest ...")
ligand_template_structure = remove_non_protein(
ligand_template_structure, exceptions=[ligand_template.ligand], remove_water=False
)
logging.debug("Superposing structure on kinase domain ...")
ligand_template_structure = superpose_proteins(kinase_domain, ligand_template_structure)
logging.debug("Adding hydrogens ...")
oechem.OEPlaceHydrogens(ligand_template_structure)
split_options = oechem.OESplitMolComplexOptions()
logging.debug("Extracting ligand ...")
ligand_template_structure = list(
oechem.OEGetMolComplexComponents(
ligand_template_structure, split_options, split_options.GetLigandFilter()
)
)[0]
return ligand_template_structure
def SplitMolComplexIterAllSitesLigName(oms, mol, ligName):
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ITER-LIGNAME-AND-ALL-SITES>
opt = oechem.OESplitMolComplexOptions(ligName)
allSites = 0
opt.ResetFilters(allSites)
for frag in oechem.OEGetMolComplexComponents(mol, opt):
# ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ITER-LIGNAME-AND-ALL-SITES>
oechem.OEWriteMolecule(oms, frag)
def SplitMolComplexIterLigName(oms, mol, ligName):
# the ligand has been identified by name
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ITER-LIGNAME>
# for input molecule mol and string ligName ...
opt = oechem.OESplitMolComplexOptions(ligName)
for frag in oechem.OEGetMolComplexComponents(mol, opt):
# ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ITER-LIGNAME>
oechem.OEWriteMolecule(oms, frag)
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!")
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)
for frag in oechem.OEGetMolComplexComponents(inmol, opts):
oechem.OEThrow.Verbose("frag %s" % frag.GetTitle())
oechem.OEWriteMolecule(oms, frag)
oms.close()
def SplitMolComplexIter(oms, mol):
# limiting lig, prot and wat to just near the first binding site
# (a very common pattern)
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ITER-SIMPLE>
# for input molecule mol ...
for frag in oechem.OEGetMolComplexComponents(mol):
# ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ITER-SIMPLE>
oechem.OEWriteMolecule(oms, frag)
# other api points illustrated below
# @ <SNIPPET-SPLIT-MOL-COMPLEX-SPLIT-COVALENT>
opt = oechem.OESplitMolComplexOptions()
opt.SetSplitCovalent()
# @ </SNIPPET-SPLIT-MOL-COMPLEX-SPLIT-COVALENT>
# @ <SNIPPET-SPLIT-MOL-FILTER-SURFACE-WATERS>
site = 1
surfaceWaters = True
opt.ResetFilters(site, surfaceWaters)
opt.SetMaxSurfaceWaterDist(8.0)
def SplitMolComplexIterFilter(oms, mol):
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ADD-COFACTOR>
db = oechem.OEResidueCategoryData()
db.AddToDB(oechem.OEResidueDatabaseCategory_Cofactor, "MTQ")
cat = oechem.OEMolComplexCategorizer()
cat.SetResidueCategoryData(db)
opt = oechem.OESplitMolComplexOptions()
opt.SetCategorizer(cat)
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ADD-COFACTOR>
# @ <SNIPPET-SPLIT-MOL-COMPLEX-ITER-FILTER>
# for input molecule mol and options opt ...
for l in oechem.OEGetMolComplexComponents(mol, opt, opt.GetLigandFilter()):
# ...
# @ </SNIPPET-SPLIT-MOL-COMPLEX-ITER-FILTER>
oechem.OEWriteMolecule(oms, l)
# @ <SNIPPET-SPLIT-MOL-COMPLEX-EXAMPLE-FILTER>
ofilter = opt.GetOtherFilter()
# @ </SNIPPET-SPLIT-MOL-COMPLEX-EXAMPLE-FILTER>
rs = oechem.OERoles()
ofilter(rs)