def process(self, ligand, port):
try:
charged_ligand = None
# Ligand sanitation
ligand = oeommutils.sanitizeOEMolecule(ligand)
if not oechem.OEHasPartialCharges(ligand):
# Charge the ligand
charged_ligand = ff_utils.assignELF10charges(
ligand, self.opt['max_conformers'], strictStereo=True)
# If the ligand has been charged then transfer the computed
# charges to the starting ligand
if charged_ligand:
map_charges = {
at.GetIdx(): at.GetPartialCharge()
for at in charged_ligand.GetAtoms()
}
for at in ligand.GetAtoms():
at.SetPartialCharge(map_charges[at.GetIdx()])
self.success.emit(ligand)
except Exception as e:
# Attach error message to the molecule that failed
self.log.error(traceback.format_exc())
ligand.SetData('error', str(e))
# Return failed mol
self.failure.emit(ligand)
return
def process(self, initialRecord, port):
try:
if not initialRecord.has_value(Fields.primary_molecule):
raise ValueError("Missing Primary Molecule field")
ligand = initialRecord.get_value(Fields.primary_molecule)
# place the entire initial record as a sub-record, to be restored when conformer runs are gathered
record = OERecord()
record.set_value(Fields.ligInit_rec, initialRecord)
if oechem.OECalculateMolecularWeight(ligand) > 1500.0: # Units are in Dalton
raise ValueError("[{}] The molecule {} seems to have a large molecular weight for a "
"ligand: {:.2f} Da)".format(self.title,
ligand.GetTitle(),
oechem.OECalculateMolecularWeight(ligand)))
# Removing Interaction Hint Container, Style and PDB Data
oechem.OEDeleteInteractionsHintSerializationData(ligand)
oechem.OEDeleteInteractionsHintSerializationIds(ligand)
oechem.OEClearStyle(ligand)
oechem.OEClearPDBData(ligand)
# Ligand sanitation
ligand = oeommutils.sanitizeOEMolecule(ligand)
lig_title = ligand.GetTitle()
if lig_title == "":
lig_title = 'LIG'
record.set_value(Fields.ligand_name, lig_title)
for at in ligand.GetAtoms():
residue = oechem.OEAtomGetResidue(at)
residue.SetName(self.args.lig_res_name)
oechem.OEAtomSetResidue(at, residue)
record.set_value(Fields.primary_molecule, ligand)
record.set_value(Fields.ligid, self.ligand_count)
self.success.emit(record)
self.ligand_count += 1
self.max_runs += ligand.NumConfs()
except Exception as e:
print("Failed to complete", str(e), flush=True)
self.opt['Logger'].info('Exception {} {}'.format(str(e), self.title))
self.log.error(traceback.format_exc())
self.failure.emit(initialRecord)
def applyffExcipients(excipients, opt):
"""
This function applies the selected force field to the
excipients
Parameters:
-----------
excipients: OEMol molecule
The excipients molecules to parametrize
opt: python dictionary
The options used to parametrize the excipients
Return:
-------
excipient_structure: Parmed structure instance
The parametrized excipient parmed structure
"""
# OpenMM topology and positions from OEMol
topology, positions = oeommutils.oemol_to_openmmTop(excipients)
# Try to apply the selected FF on the excipients
forcefield = app.ForceField(opt['protein_forcefield'])
# List of the unrecognized excipients
unmatched_res_list = forcefield.getUnmatchedResidues(topology)
# Unique unrecognized excipient names
templates = set()
for res in unmatched_res_list:
templates.add(res.name)
if templates: # Some excipients are not recognized
oechem.OEThrow.Info("The following excipients are not recognized "
"by the protein FF: {}"
"\nThey will be parametrized by using the FF: {}".format(templates, opt['other_forcefield']))
# Create a bit vector mask used to split recognized from un-recognize excipients
bv = oechem.OEBitVector(excipients.GetMaxAtomIdx())
bv.NegateBits()
# Dictionary containing the name and the parmed structures of the unrecognized excipients
unrc_excipient_structures = {}
# Dictionary used to skip already selected unrecognized excipients and count them
unmatched_excp = {}
# Ordered list of the unrecognized excipients
unmatched_res_order = []
for r_name in templates:
unmatched_excp[r_name] = 0
hv = oechem.OEHierView(excipients)
for chain in hv.GetChains():
for frag in chain.GetFragments():
for hres in frag.GetResidues():
r_name = hres.GetOEResidue().GetName()
if r_name not in unmatched_excp:
continue
else:
unmatched_res_order.append(r_name)
if unmatched_excp[r_name]: # Test if we have selected the unknown excipient
# Set Bit mask
atms = hres.GetAtoms()
for at in atms:
bv.SetBitOff(at.GetIdx())
unmatched_excp[r_name] += 1
else:
unmatched_excp[r_name] = 1
# Create AtomBondSet to extract from the whole excipient system
# the current selected FF unknown excipient
atms = hres.GetAtoms()
bond_set = set()
for at in atms:
bv.SetBitOff(at.GetIdx())
bonds = at.GetBonds()
for bond in bonds:
bond_set.add(bond)
atom_bond_set = oechem.OEAtomBondSet(atms)
for bond in bond_set:
atom_bond_set.AddBond(bond)
# Create the unrecognized excipient OEMol
unrc_excp = oechem.OEMol()
if not oechem.OESubsetMol(unrc_excp, excipients, atom_bond_set):
oechem.OEThrow.Fatal("Is was not possible extract the residue: {}".format(r_name))
# Charge the unrecognized excipient
if not oequacpac.OEAssignCharges(unrc_excp,
oequacpac.OEAM1BCCCharges(symmetrize=True)):
oechem.OEThrow.Fatal("Is was not possible to "
"charge the extract residue: {}".format(r_name))
# If GAFF or GAFF2 is selected as FF check for tleap command
if opt['other_forcefield'] in ['GAFF', 'GAFF2']:
ff_utils.ParamLigStructure(oechem.OEMol(), opt['other_forcefield']).checkTleap
if opt['other_forcefield'] == 'SMIRNOFF':
unrc_excp = oeommutils.sanitizeOEMolecule(unrc_excp)
# Parametrize the unrecognized excipient by using the selected FF
pmd = ff_utils.ParamLigStructure(unrc_excp, opt['other_forcefield'],
prefix_name=opt['prefix_name']+'_'+r_name)
unrc_excp_struc = pmd.parameterize()
unrc_excp_struc.residues[0].name = r_name
unrc_excipient_structures[r_name] = unrc_excp_struc
# Recognized FF excipients
pred_rec = oechem.OEAtomIdxSelected(bv)
rec_excp = oechem.OEMol()
oechem.OESubsetMol(rec_excp, excipients, pred_rec)
if rec_excp.NumAtoms() > 0:
top_known, pos_known = oeommutils.oemol_to_openmmTop(rec_excp)
ff_rec = app.ForceField(opt['protein_forcefield'])
try:
omm_system = ff_rec.createSystem(top_known, rigidWater=False)
rec_struc = parmed.openmm.load_topology(top_known, omm_system, xyz=pos_known)
except:
oechem.OEThrow.Fatal("Error in the recognised excipient parametrization")
# Unrecognized FF excipients
bv.NegateBits()
pred_unrc = oechem.OEAtomIdxSelected(bv)
unrc_excp = oechem.OEMol()
oechem.OESubsetMol(unrc_excp, excipients, pred_unrc)
# Unrecognized FF excipients coordinates
oe_coord_dic = unrc_excp.GetCoords()
unrc_coords = np.ndarray(shape=(unrc_excp.NumAtoms(), 3))
for at_idx in oe_coord_dic:
unrc_coords[at_idx] = oe_coord_dic[at_idx]
# It is important the order used to assemble the structures. In order to
# avoid mismatch between the coordinates and the structures, it is convenient
# to use the unrecognized residue order
unmatched_res_order_count = []
i = 0
while i < len(unmatched_res_order):
res_name = unmatched_res_order[i]
for j in range(i+1, len(unmatched_res_order)):
if unmatched_res_order[j] == res_name:
continue
else:
break
if i == (len(unmatched_res_order) - 1):
num = 1
unmatched_res_order_count.append((res_name, num))
break
else:
num = j - i
unmatched_res_order_count.append((res_name, num))
i = j
# Merge all the unrecognized Parmed structure
unrc_struc = parmed.Structure()
for pair in unmatched_res_order_count:
res_name = pair[0]
nums = pair[1]
unrc_struc = unrc_struc + nums*unrc_excipient_structures[res_name]
# Set the unrecognized coordinates
unrc_struc.coordinates = unrc_coords
# Set the parmed excipient structure merging
# the unrecognized and recognized parmed
# structures together
if rec_excp.NumAtoms() > 0:
excipients_structure = unrc_struc + rec_struc
else:
excipients_structure = unrc_struc
return excipients_structure
else: # All the excipients are recognized by the selected FF
omm_system = forcefield.createSystem(topology, rigidWater=False)
excipients_structure = parmed.openmm.load_topology(topology, omm_system, xyz=positions)
return excipients_structure