def renumber_structure(target_structure: oechem.OEGraphMol,
residue_numbers: List[int]) -> oechem.OEGraphMol:
"""
Renumber the residues of a protein structure according to the given list of residue numbers.
Parameters
----------
target_structure: oechem.OEGraphMol
An OpenEye molecule holding the protein structure to renumber.
residue_numbers: list of int
A list of residue numbers matching the order of the target structure.
Returns
-------
renumbered_structure: oechem.OEGraphMol
An OpenEye molecule holding the cropped protein structure.
"""
import copy
renumbered_structure = copy.deepcopy(
target_structure) # don't touch input structure
hierview = oechem.OEHierView(renumbered_structure)
structure_residues = hierview.GetResidues()
for residue_number, structure_residue in zip(residue_numbers,
structure_residues):
structure_residue_mod = structure_residue.GetOEResidue()
structure_residue_mod.SetResidueNumber(residue_number)
for residue_atom in structure_residue.GetAtoms():
oechem.OEAtomSetResidue(residue_atom, structure_residue_mod)
return renumbered_structure
def setup_yank_calculation(receptor_file_name,
ligand_file_name,
setup_directory_name,
solvate=False):
# Cleanup setup directory
if os.path.exists(setup_directory_name):
shutil.rmtree(setup_directory_name)
os.makedirs(setup_directory_name)
# Read ligand and receptor molecule
ifs_mol2 = oechem.oemolistream()
ifs_mol2.open(ligand_file_name)
ligand_oemol = oechem.OEGraphMol()
oechem.OEReadMolecule(ifs_mol2, ligand_oemol)
ifs_mol2.close()
ifs_mol2 = oechem.oemolistream()
ifs_mol2.open(receptor_file_name)
receptor_oemol = oechem.OEGraphMol()
oechem.OEReadMolecule(ifs_mol2, receptor_oemol)
ifs_mol2.close()
# Push ligand close to receptor
pull_close(receptor_oemol, ligand_oemol, MIN_DISTANCE, MAX_DISTANCE)
# Add residue name 'MOL'
residue = oechem.OEResidue()
residue.SetName('MOL')
for atom in ligand_oemol.GetAtoms():
oechem.OEAtomSetResidue(atom, residue)
# Parametrize ligand
with working_directory(setup_directory_name):
# Save translated ligand
ofs = oechem.oemolostream()
ofs.open('ligand.mol2')
oechem.OEWriteMolecule(ofs, ligand_oemol)
ofs.close()
# Parametrize ligand
print "Parameterizing ligand with GAFF..."
run_command(
'antechamber -fi mol2 -i ligand.mol2 -fo mol2 -o ligand.gaff.mol2')
run_command(
'parmchk -i ligand.gaff.mol2 -o ligand.gaff.frcmod -f mol2')
# Copy receptor so that leap will know the PDB file name
shutil.copyfile(receptor_file_name, 'receptor.pdb')
# Create AMBER prmtop/inpcrd files.
print "Creating AMBER prmtop/inpcrd files..."
cmd = 'tleap -f {!s} > setup.leap.out'
if solvate:
run_command(cmd.format(LEAP_IN_EXPLICIT))
else:
run_command(cmd.format(LEAP_IN_IMPLICIT))
def __iter__(self):
max_idx = self.args.limit
if max_idx is not None:
max_idx = int(max_idx)
count = 0
self.config = config_from_env()
in_orion = self.config is not None
if not in_orion:
with oechem.oemolistream(str(self.args.data_in)) as ifs:
for mol in ifs.GetOEMols():
mol.SetData(oechem.OEGetTag('prefix'), self.opt['prefix'])
mol.SetData(oechem.OEGetTag('suffix'), self.opt['suffix'])
for at in mol.GetAtoms():
residue = oechem.OEAtomGetResidue(at)
residue.SetName(self.opt['type'])
oechem.OEAtomSetResidue(at, residue)
if self.opt['IDTag']:
mol.SetData(oechem.OEGetTag('IDTag'), 'l' + mol.GetTitle()[0:12] + '_' + str(count))
yield mol
count += 1
if max_idx is not None and count == max_idx:
break
else:
stream = StreamingDataset(self.args.data_in,
input_format=self.args.download_format)
for mol in stream:
mol.SetData(oechem.OEGetTag('prefix'), self.opt['prefix'])
mol.SetData(oechem.OEGetTag('suffix'), self.opt['suffix'])
for at in mol.GetAtoms():
residue = oechem.OEAtomGetResidue(at)
residue.SetName(self.opt['type'])
oechem.OEAtomSetResidue(at, residue)
if self.opt['IDTag']:
mol.SetData(oechem.OEGetTag('IDTag'), 'l' + mol.GetTitle()[0:12] + '_'+str(count))
yield mol
count += 1
if max_idx is not None and count == max_idx:
break
def update_residue_identifiers(
structure: oechem.OEGraphMol,
keep_protein_residue_ids: bool = True) -> oechem.OEGraphMol:
"""
Updates the atom, residue and chain ids of the given molecular structure. All residues become part of chain A. Atom
ids will start from 1. Residue will start from 1, except protein residue ids are fixed. This is especially useful,
if molecules were merged, which can result in overlapping atom and residue ids as well as separate chains.
Parameters
----------
structure: oechem.OEGraphMol
The OpenEye molecule structure for updating atom and residue ids.
keep_protein_residue_ids: bool
If the protein residues should be kept.
Returns
-------
structure: oechem.OEGraphMol
The OpenEye molecule structure with updated atom and residue ids.
"""
# update residue ids
residue_number = 0
hierarchical_view = oechem.OEHierView(structure)
for hv_residue in hierarchical_view.GetResidues():
residue = hv_residue.GetOEResidue()
residue.SetChainID("A")
if not residue.IsHetAtom() and keep_protein_residue_ids:
if residue.GetName() == "NME" and residue.GetResidueNumber(
) == residue_number:
# NME residues may have same id as preceding residue
residue_number += 1
else:
# catch protein residue id if those should not be touched
residue_number = residue.GetResidueNumber()
else:
# change residue id
residue_number += 1
residue.SetResidueNumber(residue_number)
for atom in hv_residue.GetAtoms():
oechem.OEAtomSetResidue(atom, residue)
# update residue identifiers, except atom names, residue ids,
# residue names, fragment number, chain id and record type
preserved_info = (oechem.OEPreserveResInfo_ResidueNumber
| oechem.OEPreserveResInfo_ResidueName
| oechem.OEPreserveResInfo_HetAtom
| oechem.OEPreserveResInfo_AtomName
| oechem.OEPreserveResInfo_FragmentNumber
| oechem.OEPreserveResInfo_ChainID)
oechem.OEPerceiveResidues(structure, preserved_info)
return structure
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 _OEFixBuiltLoopFragmentNumbers(protein):
"""
Temporary fix, thanks to Jesper!
"""
prev_fn = -1
# Checking for CA atoms, since this will avoid messing with the caps and built sidechains,
# since this is only a built loop problem
builtPred = oespruce.OEIsModeledAtom()
for atom in protein.GetAtoms(oechem.OEIsCAlpha()):
res = oechem.OEAtomGetResidue(atom)
fn = res.GetFragmentNumber()
if builtPred(atom) and prev_fn != -1:
for ra in oechem.OEGetResidueAtoms(atom):
r = oechem.OEAtomGetResidue(ra)
r.SetFragmentNumber(prev_fn)
oechem.OEAtomSetResidue(ra, r)
else:
prev_fn = fn
def Rename(ims, oms):
for mol in ims.GetOEGraphMols():
# @ <SNIPPET-PERCEIVE-RES>
if not oechem.OEHasResidues(mol):
oechem.OEPerceiveResidues(mol, oechem.OEPreserveResInfo_All)
# @ </SNIPPET-PERCEIVE-RES>
# @ <SNIPPET-MSE-TO-MET-CORE>
for atom in mol.GetAtoms():
thisRes = oechem.OEAtomGetResidue(atom)
if oechem.OEGetResidueIndex(thisRes) == oechem.OEResidueIndex_MSE:
thisRes.SetName("MET") # modify res properties
thisRes.SetHetAtom(False)
oechem.OEAtomSetResidue(atom, thisRes) # store updated residue
if atom.GetAtomicNum() == oechem.OEElemNo_Se:
atom.SetAtomicNum(
oechem.OEElemNo_S) # fix atom type & name
atom.SetName(" SD ")
# @ </SNIPPET-MSE-TO-MET-CORE>
oechem.OEWriteMolecule(oms, mol)
def _OEFixWaterFragmentNumbers(solvent):
"""
Temporary fix, thanks to Jesper!
"""
fragment_counter = {}
for atom in solvent.GetAtoms(oechem.OEIsWater()):
res = oechem.OEAtomGetResidue(atom)
if res.GetInsertCode() != " ":
continue
if res.GetFragmentNumber() not in fragment_counter:
fragment_counter[res.GetFragmentNumber()] = 0
fragment_counter[res.GetFragmentNumber()] += 1
largest_solvent_fn_count = -1
largest_solvent_fn = -1
for fn in fragment_counter:
if fragment_counter[fn] > largest_solvent_fn_count:
largest_solvent_fn_count = fragment_counter[fn]
largest_solvent_fn = fn
if largest_solvent_fn < 0:
return
for atom in solvent.GetAtoms(oechem.OEIsWater(True)):
res = oechem.OEAtomGetResidue(atom)
res.SetFragmentNumber(largest_solvent_fn)
oechem.OEAtomSetResidue(atom, res)
def enumerate_conformations(name, smiles=None, pdbname=None):
"""Run Epik to get protonation states using PDB residue templates for naming.
Parameters
----------
name : str
Common name of molecule (used to create subdirectory)
smiles : str
Isomeric SMILES string
pdbname : str
Three-letter PDB code (e.g. 'DB8')
"""
# Create output subfolder
output_basepath = os.path.join(output_dir, name)
if not os.path.isdir(output_basepath):
os.mkdir(output_basepath)
output_basepath = os.path.join(output_basepath, name)
if pdbname:
# Make sure to only use one entry if there are mutliple
if ' ' in pdbname:
pdbnames = pdbname.split(' ')
print("Splitting '%s' into first entry only: '%s'" % (pdbname, pdbnames[0]))
pdbname = pdbnames[0]
# Retrieve PDB (for atom names)
url = 'http://ligand-expo.rcsb.org/reports/%s/%s/%s_model.pdb' % (pdbname[0], pdbname, pdbname)
pdb_filename = output_basepath + '-input.pdb'
retrieve_url(url, pdb_filename)
pdb_molecule = read_molecule(pdb_filename)
# Retrieve SDF (for everything else)
url = 'http://ligand-expo.rcsb.org/reports/%s/%s/%s_model.sdf' % (pdbname[0], pdbname, pdbname)
sdf_filename = output_basepath + '-input.sdf'
retrieve_url(url, sdf_filename)
sdf_molecule = read_molecule(sdf_filename)
# Replace atom names in SDF
for (sdf_atom, pdb_atom) in zip(sdf_molecule.GetAtoms(), pdb_molecule.GetAtoms()):
sdf_atom.SetName(pdb_atom.GetName())
# Assign Tripos atom types
oechem.OETriposAtomTypeNames(sdf_molecule)
oechem.OETriposBondTypeNames(sdf_molecule)
oe_molecule = sdf_molecule
# We already know the residue name
residue_name = pdbname
elif smiles:
# Generate molecule geometry with OpenEye
print("Generating molecule {}".format(name))
oe_molecule = openeye.smiles_to_oemol(smiles)
# Assign Tripos atom types
oechem.OETriposAtomTypeNames(oe_molecule)
oechem.OETriposBondTypeNames(oe_molecule)
try:
oe_molecule = openeye.get_charges(oe_molecule, keep_confs=1)
except RuntimeError as e:
traceback.print_exc()
print("Skipping molecule " + name)
return
residue_name = re.sub('[^A-Za-z]+', '', name.upper())[:3]
else:
raise Exception('Must provide SMILES string or pdbname')
# Save mol2 file, preserving atom names
print("Running epik on molecule {}".format(name))
mol2_file_path = output_basepath + '-input.mol2'
write_mol2_preserving_atomnames(mol2_file_path, oe_molecule, residue_name)
# Run epik on mol2 file
mae_file_path = output_basepath + '-epik.mae'
schrodinger.run_epik(mol2_file_path, mae_file_path, tautomerize=False,
max_structures=100, min_probability=np.exp(-MAX_ENERGY_PENALTY), ph=7.4)
# Convert maestro file to sdf and mol2
output_sdf_filename = output_basepath + '-epik.sdf'
output_mol2_filename = output_basepath + '-epik.mol2'
schrodinger.run_structconvert(mae_file_path, output_sdf_filename)
schrodinger.run_structconvert(mae_file_path, output_mol2_filename)
# Read SDF file.
ifs_sdf = oechem.oemolistream()
ifs_sdf.SetFormat(oechem.OEFormat_SDF)
ifs_sdf.open(output_sdf_filename)
sdf_molecule = oechem.OEGraphMol()
# Read MOL2 file.
ifs_mol2 = oechem.oemolistream()
ifs_mol2.open(output_mol2_filename)
mol2_molecule = oechem.OEMol()
# Assign charges.
charged_molecules = list()
index = 0
while oechem.OEReadMolecule(ifs_sdf, sdf_molecule):
oechem.OEReadMolecule(ifs_mol2, mol2_molecule)
index += 1
print("Charging molecule %d" % (index))
try:
# Charge molecule.
charged_molecule = openeye.get_charges(mol2_molecule, max_confs=800, strictStereo=False, normalize=True, keep_confs=None)
# Assign Tripos types
oechem.OETriposAtomTypeNames(charged_molecule)
oechem.OETriposBondTypeNames(charged_molecule)
# Store tags.
oechem.OECopySDData(charged_molecule, sdf_molecule)
# Store molecule
charged_molecules.append(charged_molecule)
except Exception as e:
print(e)
print("Skipping protomer/tautomer because of failed charging.")
# Clean up
ifs_sdf.close()
ifs_mol2.close()
# Write state penalites.
outfile = open(output_basepath + '-state-penalties.out', 'w')
for (index, charged_molecule) in enumerate(charged_molecules):
# Get Epik data.
epik_Ionization_Penalty = float(oechem.OEGetSDData(charged_molecule, "r_epik_Ionization_Penalty"))
epik_Ionization_Penalty_Charging = float(oechem.OEGetSDData(charged_molecule, "r_epik_Ionization_Penalty_Charging"))
epik_Ionization_Penalty_Neutral = float(oechem.OEGetSDData(charged_molecule, "r_epik_Ionization_Penalty_Neutral"))
epik_State_Penalty = float(oechem.OEGetSDData(charged_molecule, "r_epik_State_Penalty"))
epik_Tot_Q = int(oechem.OEGetSDData(charged_molecule, "i_epik_Tot_Q"))
outfile.write('%16.8f\n' % epik_State_Penalty)
outfile.close()
# Write as PDB
charged_pdb_filename = output_basepath + '-epik-charged.pdb'
ofs = oechem.oemolostream(charged_pdb_filename)
flavor = oechem.OEOFlavor_PDB_CurrentResidues | oechem.OEOFlavor_PDB_ELEMENT | oechem.OEOFlavor_PDB_BONDS | oechem.OEOFlavor_PDB_HETBONDS | oechem.OEOFlavor_PDB_BOTH
ofs.SetFlavor(oechem.OEFormat_PDB, flavor)
for (index, charged_molecule) in enumerate(charged_molecules):
# Fix residue names
for atom in charged_molecule.GetAtoms():
residue = oechem.OEAtomGetResidue(atom)
residue.SetName(residue_name)
oechem.OEAtomSetResidue(atom, residue)
#oechem.OEWritePDBFile(ofs, charged_molecule, flavor)
oechem.OEWriteMolecule(ofs, charged_molecule)
ofs.close()
# Write molecules as mol2.
charged_mol2_filename = output_basepath + '-epik-charged.mol2'
write_mol2_preserving_atomnames(charged_mol2_filename, charged_molecules, residue_name)
def process(self, mol, port):
try:
# Split the complex in components in order to apply the FF
protein, ligand, water, excipients = utils.split(mol)
# Unique prefix name used to output parametrization files
self.opt['prefix_name'] = mol.GetTitle()
# Apply FF to the Protein
protein_structure = utils.applyffProtein(protein, self.opt)
# Apply FF to water molecules
water_structure = utils.applyffWater(water, self.opt)
# Apply FF to the excipients
if excipients.NumAtoms() > 0:
excipient_structure = utils.applyffExcipients(excipients, self.opt)
# The excipient order is set equal to the order in related
# parmed structure to avoid possible atom index mismatching
excipients = oeommutils.openmmTop_to_oemol(excipient_structure.topology,
excipient_structure.positions,
verbose=False)
# Apply FF to the ligand
ligand_structure = utils.applyffLigand(ligand, self.opt)
# Build the Parmed structure
if excipients.NumAtoms() > 0:
complex_structure = protein_structure + ligand_structure + \
excipient_structure + water_structure
else:
complex_structure = protein_structure + ligand_structure + water_structure
num_atom_system = protein.NumAtoms() + ligand.NumAtoms() + excipients.NumAtoms() + water.NumAtoms()
if not num_atom_system == complex_structure.topology.getNumAtoms():
oechem.OEThrow.Fatal("Parmed and OE topologies mismatch atom number error")
# Assemble a new OEMol complex in a specific order
# to match the defined Parmed structure complex
complx = protein.CreateCopy()
oechem.OEAddMols(complx, ligand)
oechem.OEAddMols(complx, excipients)
oechem.OEAddMols(complx, water)
complx.SetTitle(mol.GetTitle())
# Set Parmed structure box_vectors
vec_data = pack_utils.PackageOEMol.getData(complx, tag='box_vectors')
vec = pack_utils.PackageOEMol.decodePyObj(vec_data)
complex_structure.box_vectors = vec
# Attach the Parmed structure to the complex
packed_complex = pack_utils.PackageOEMol.pack(complx, complex_structure)
# Attach the reference positions to the complex
ref_positions = complex_structure.positions
packedpos = pack_utils.PackageOEMol.encodePyObj(ref_positions)
packed_complex.SetData(oechem.OEGetTag('OEMDDataRefPositions'), packedpos)
# Set atom serial numbers, Ligand name and HETATM flag
# oechem.OEPerceiveResidues(packed_complex, oechem.OEPreserveResInfo_SerialNumber)
for at in packed_complex.GetAtoms():
thisRes = oechem.OEAtomGetResidue(at)
thisRes.SetSerialNumber(at.GetIdx())
if thisRes.GetName() == 'UNL':
thisRes.SetName("LIG")
thisRes.SetHetAtom(True)
oechem.OEAtomSetResidue(at, thisRes)
if packed_complex.GetMaxAtomIdx() != complex_structure.topology.getNumAtoms():
raise ValueError("OEMol complex and Parmed structure mismatch atom numbers")
# Check if it is possible to create the OpenMM System
system = complex_structure.createSystem(nonbondedMethod=app.CutoffPeriodic,
nonbondedCutoff=10.0 * unit.angstroms,
constraints=app.HBonds,
removeCMMotion=False)
self.success.emit(packed_complex)
except Exception as e:
# Attach error message to the molecule that failed
self.log.error(traceback.format_exc())
mol.SetData('error', str(e))
# Return failed mol
self.failure.emit(mol)
return
def process(self, mol, port):
try:
# Split the complex in components in order to apply the FF
protein, ligand, water, excipients = oeommutils.split(
mol, ligand_res_name=self.opt['ligand_res_name'])
self.log.info(
"\nComplex name: {}\nProtein atom numbers = {}\nLigand atom numbers = {}\n"
"Water atom numbers = {}\nExcipients atom numbers = {}".format(
mol.GetTitle(), protein.NumAtoms(), ligand.NumAtoms(),
water.NumAtoms(), excipients.NumAtoms()))
# Unique prefix name used to output parametrization files
self.opt['prefix_name'] = mol.GetTitle()
oe_mol_list = []
par_mol_list = []
# Apply FF to the Protein
if protein.NumAtoms():
oe_mol_list.append(protein)
protein_structure = utils.applyffProtein(protein, self.opt)
par_mol_list.append(protein_structure)
# Apply FF to the ligand
if ligand.NumAtoms():
oe_mol_list.append(ligand)
ligand_structure = utils.applyffLigand(ligand, self.opt)
par_mol_list.append(ligand_structure)
# Apply FF to water molecules
if water.NumAtoms():
oe_mol_list.append(water)
water_structure = utils.applyffWater(water, self.opt)
par_mol_list.append(water_structure)
# Apply FF to the excipients
if excipients.NumAtoms():
excipient_structure = utils.applyffExcipients(
excipients, self.opt)
par_mol_list.append(excipient_structure)
# The excipient order is set equal to the order in related
# parmed structure to avoid possible atom index mismatching
excipients = oeommutils.openmmTop_to_oemol(
excipient_structure.topology,
excipient_structure.positions,
verbose=False)
oechem.OEPerceiveBondOrders(excipients)
oe_mol_list.append(excipients)
# Build the overall Parmed structure
complex_structure = parmed.Structure()
for struc in par_mol_list:
complex_structure = complex_structure + struc
complx = oe_mol_list[0].CreateCopy()
num_atom_system = complx.NumAtoms()
for idx in range(1, len(oe_mol_list)):
oechem.OEAddMols(complx, oe_mol_list[idx])
num_atom_system += oe_mol_list[idx].NumAtoms()
if not num_atom_system == complex_structure.topology.getNumAtoms():
oechem.OEThrow.Fatal(
"Parmed and OE topologies mismatch atom number error")
complx.SetTitle(mol.GetTitle())
# Set Parmed structure box_vectors
is_periodic = True
try:
vec_data = pack_utils.PackageOEMol.getData(complx,
tag='box_vectors')
vec = pack_utils.PackageOEMol.decodePyObj(vec_data)
complex_structure.box_vectors = vec
except:
is_periodic = False
self.log.warn(
"System has been parametrize without periodic box vectors for vacuum simulation"
)
# Attach the Parmed structure to the complex
packed_complex = pack_utils.PackageOEMol.pack(
complx, complex_structure)
# Attach the reference positions to the complex
ref_positions = complex_structure.positions
packedpos = pack_utils.PackageOEMol.encodePyObj(ref_positions)
packed_complex.SetData(oechem.OEGetTag('OEMDDataRefPositions'),
packedpos)
# Set atom serial numbers, Ligand name and HETATM flag
# oechem.OEPerceiveResidues(packed_complex, oechem.OEPreserveResInfo_SerialNumber)
for at in packed_complex.GetAtoms():
thisRes = oechem.OEAtomGetResidue(at)
thisRes.SetSerialNumber(at.GetIdx())
if thisRes.GetName() == 'UNL':
# thisRes.SetName("LIG")
thisRes.SetHetAtom(True)
oechem.OEAtomSetResidue(at, thisRes)
if packed_complex.GetMaxAtomIdx(
) != complex_structure.topology.getNumAtoms():
raise ValueError(
"OEMol complex and Parmed structure mismatch atom numbers")
# Check if it is possible to create the OpenMM System
if is_periodic:
complex_structure.createSystem(
nonbondedMethod=app.CutoffPeriodic,
nonbondedCutoff=10.0 * unit.angstroms,
constraints=app.HBonds,
removeCMMotion=False)
else:
complex_structure.createSystem(nonbondedMethod=app.NoCutoff,
constraints=app.HBonds,
removeCMMotion=False)
self.success.emit(packed_complex)
except Exception as e:
# Attach error message to the molecule that failed
self.log.error(traceback.format_exc())
mol.SetData('error', str(e))
# Return failed mol
self.failure.emit(mol)
return
def openmmTop_to_oemol(topology, positions, verbose=False):
"""
This function converts an OpenMM topology in an OEMol
Parameters:
-----------
topology : OpenMM Topology
The OpenMM topology
positions : OpenMM Quantity
The molecule atom positions associated with the
topology
Return:
-------
oe_mol : OEMol
The generated OEMol molecule
"""
# Create an empty OEMol
oe_mol = oechem.OEMol()
# Mapping dictionary between openmm atoms and oe atoms
openmm_atom_to_oe_atom = {}
# Python set used to identify atoms that are not in protein residues
keep = set(proteinResidues).union(dnaResidues).union(rnaResidues)
for chain in topology.chains():
for res in chain.residues():
# Create an OEResidue
oe_res = oechem.OEResidue()
# Set OEResidue name
oe_res.SetName(res.name)
# If the atom is not a protein atom then set its heteroatom
# flag to True
if res.name not in keep:
oe_res.SetFragmentNumber(chain.index + 1)
oe_res.SetHetAtom(True)
# Set OEResidue Chain ID
oe_res.SetChainID(chain.id)
# res_idx = int(res.id) - chain.index * len(chain._residues)
# Set OEResidue number
oe_res.SetResidueNumber(int(res.id))
for openmm_at in res.atoms():
# Create an OEAtom based on the atomic number
oe_atom = oe_mol.NewAtom(openmm_at.element._atomic_number)
# Set atom name
oe_atom.SetName(openmm_at.name)
# Set Symbol
oe_atom.SetType(openmm_at.element.symbol)
# Set Atom index
oe_res.SetSerialNumber(openmm_at.index + 1)
# Commit the changes
oechem.OEAtomSetResidue(oe_atom, oe_res)
# Update the dictionary OpenMM to OE
openmm_atom_to_oe_atom[openmm_at] = oe_atom
if topology.getNumAtoms() != oe_mol.NumAtoms():
raise ValueError(
"OpenMM topology and OEMol number of atoms mismatching: "
"OpenMM = {} vs OEMol = {}".format(topology.getNumAtoms(),
oe_mol.NumAtoms()))
# Count the number of bonds in the openmm topology
omm_bond_count = 0
# Create the bonds
for omm_bond in topology.bonds():
omm_bond_count += 1
at0 = omm_bond[0]
at1 = omm_bond[1]
oe_bond_order = omm_bond.order
# If bond order info are not present set the bond order temporary to one
if not omm_bond.order:
oe_bond_order = 1
# OE atoms
oe_atom0 = openmm_atom_to_oe_atom[at0]
oe_atom1 = openmm_atom_to_oe_atom[at1]
# Create the bond
oe_bond = oe_mol.NewBond(oe_atom0, oe_atom1, oe_bond_order)
if omm_bond.type:
if omm_bond.type == 'Aromatic':
oe_atom0.SetAromatic(True)
oe_atom1.SetAromatic(True)
oe_bond.SetAromatic(True)
oe_bond.SetType("Aromatic")
elif omm_bond.type in ["Single", "Double", "Triple", "Amide"]:
oe_bond.SetType(omm_bond.type)
else:
oe_bond.SetType("")
if omm_bond_count != oe_mol.NumBonds():
raise ValueError(
"OpenMM topology and OEMol number of bonds mismatching: "
"OpenMM = {} vs OEMol = {}".format(omm_bond_count,
oe_mol.NumBonds()))
# Set the OEMol positions
pos = positions.in_units_of(unit.angstrom) / unit.angstrom
pos = list(itertools.chain.from_iterable(pos))
oe_mol.SetCoords(pos)
oechem.OESetDimensionFromCoords(oe_mol)
return oe_mol
def enumerate_conformations(name,
pdbfile=None,
smiles=None,
pdbname=None,
pH=7.4):
"""Run Epik to get protonation states using PDB residue templates for naming.
Parameters
----------
name : str
Common name of molecule (used to create subdirectory)
smiles : str
Isomeric SMILES string
pdbname : str
Three-letter PDB code (e.g. 'DB8')
"""
# Create output subfolder
# output_basepath = os.path.join(output_dir, name)
# if not os.path.isdir(output_basepath):
# os.mkdir(output_basepath)
# output_basepath = os.path.join(output_basepath, name)
oehandler = openeye.oechem.OEThrow
# String stream output
oss = oechem.oeosstream()
oehandler.SetOutputStream(oss)
log = "New run:\nPDB code: {pdbname}; Molecule: {name}; pH {pH}\n".format(
**locals())
success_status = True
if pdbname:
# Make sure to only use one entry if there are multiple
if ' ' in pdbname:
pdbnames = pdbname.split(' ')
log += "Splitting '%s' into first entry only: '%s'" % (pdbname,
pdbnames[0])
pdbname = pdbnames[0]
# Retrieve PDB (for atom names)
url = 'http://ligand-expo.rcsb.org/reports/%s/%s/%s_model.pdb' % (
pdbname[0], pdbname, pdbname)
pdb_filename = name + '-rcsb_download.pdb'
log += "Retrieving PDB structure from RCSB ligand expo: {}.\n".format(
pdb_filename)
retrieve_url(url, pdb_filename)
log += "Parsing PDB file.\n"
pdb_molecule = read_molecule(pdb_filename)
# Retrieve SDF (for everything else)
url = 'http://ligand-expo.rcsb.org/reports/%s/%s/%s_model.sdf' % (
pdbname[0], pdbname, pdbname)
sdf_filename = name + '-rcsb_download.sdf'
log += "Retrieving SDF structure from RCSB ligand expo: {}.\n".format(
sdf_filename)
retrieve_url(url, sdf_filename)
log += "Parsing SDF file.\n"
sdf_molecule = read_molecule(sdf_filename)
# Replace atom names in SDF
log += "Canonicalizing atom names.\n"
for (sdf_atom, pdb_atom) in zip(sdf_molecule.GetAtoms(),
pdb_molecule.GetAtoms()):
sdf_atom.SetName(pdb_atom.GetName())
# Assign Tripos atom types
log += "Assign atom type names.\n"
oechem.OETriposAtomTypeNames(sdf_molecule)
oechem.OETriposBondTypeNames(sdf_molecule)
oe_molecule = sdf_molecule
# We already know the residue name
residue_name = pdbname
# For the moment, disabling these two types of input
# elif smiles:
# # Generate molecule geometry with OpenEye
# logging.info(("Generating molecule {}".format(name)))
# oe_molecule = openeye.smiles_to_oemol(smiles)
# # Assign Tripos atom types
# oechem.OETriposAtomTypeNames(oe_molecule)
# oechem.OETriposBondTypeNames(oe_molecule)
# try:
# logging.info("Charging initial")
# write_mol2_preserving_atomnames(name + '-debug.mol2', oe_molecule, 'debug')
# oe_molecule = openeye.get_charges(oe_molecule, keep_confs=1)
# except RuntimeError as e:
# traceback.print_exc()
# logging.info(("Skipping molecule " + name))
# return
# residue_name = re.sub('[^A-Za-z]+', '', name.upper())[:3]
# logging.info("resname = %s", residue_name)
# oe_molecule.SetTitle(residue_name) # fix iupac name issue with mol2convert
# elif pdbfile:
# residue_name = re.sub('[^A-Za-z]+', '', name.upper())[:3]
# logging.info("Loading molecule molecule {0} from {1}".format(name, pdbfile))
# oe_molecule = read_molecule(pdbfile)
# # Assign Tripos atom types
# oechem.OETriposAtomTypeNames(oe_molecule)
# oechem.OETriposBondTypeNames(oe_molecule)
# try:
# logging.info("Charging initial")
# write_mol2_preserving_atomnames(name + '-debug.mol2', oe_molecule, 'debug')
# oe_molecule = openeye.get_charges(oe_molecule, keep_confs=1)
# except RuntimeError as e:
# traceback.print_exc()
# logging.info(("Skipping molecule " + name))
# return
else:
raise Exception('Must provide SMILES string or pdbname, or pdbfile')
# Save mol2 file, preserving atom names
log += "Running Epik.\n"
mol2_file_path = name + '-before_epik.mol2'
write_mol2_preserving_atomnames(mol2_file_path, oe_molecule, residue_name)
# Run epik on mol2 file
mae_file_path = name + '-epik.mae'
schrodinger.run_epik(mol2_file_path,
mae_file_path,
tautomerize=False,
max_structures=50,
min_probability=np.exp(-MAX_ENERGY_PENALTY),
ph=pH)
log += "Epik run completed.\n"
# Convert maestro file to sdf and mol2
output_sdf_filename = name + '-after_epik.sdf'
output_mol2_filename = name + '-after_epik.mol2'
# logging.info("Creating sdf")
schrodinger.run_structconvert(mae_file_path, output_sdf_filename)
# logging.info("Creating mol2")
schrodinger.run_structconvert(mae_file_path, output_mol2_filename)
# Read SDF file.
ifs_sdf = oechem.oemolistream()
ifs_sdf.SetFormat(oechem.OEFormat_SDF)
ifs_sdf.open(output_sdf_filename)
sdf_molecule = oechem.OEGraphMol()
# Read MOL2 file.
ifs_mol2 = oechem.oemolistream()
ifs_mol2.open(output_mol2_filename)
mol2_molecule = oechem.OEMol()
# Assign charges.
# reset count of error handler
oehandler.Clear()
log += "Assigning charges to protonation states.\n"
charged_molecules = list()
index = 0
failed_states = set()
while oechem.OEReadMolecule(ifs_sdf, sdf_molecule):
oechem.OEReadMolecule(ifs_mol2, mol2_molecule)
index += 1
log += "State {0:d}\n".format(index)
try:
# Charge molecule.
charged_molecule_conformers = omtoe.get_charges(mol2_molecule,
max_confs=800,
strictStereo=False,
normalize=True,
keep_confs=-1)
log += "Charging stage output:\n"
OEOutput = str(oss)
log += OEOutput
log += "\nCharging state completed.\n"
# Restore coordinates to original
charged_molecule = select_conformers(charged_molecule_conformers,
mol2_molecule,
keep_confs=None)
# Assign Tripos types
oechem.OETriposAtomTypeNames(charged_molecule)
oechem.OETriposBondTypeNames(charged_molecule)
# Store tags.
oechem.OECopySDData(charged_molecule, sdf_molecule)
# Store molecule
charged_molecules.append(charged_molecule)
# Check for failure in the log
openeye_charge_log_parser(OEOutput, True)
oehandler.Clear()
except Exception as e:
failed_states.add(index)
logging.info(e)
log += "State failed charging.\n"
log += str(e)
log += "\n"
filename_failure = name + '-conformers-failed-state-{}-.mol2'.format(
index)
try:
write_mol2_preserving_atomnames(filename_failure,
charged_molecule_conformers,
residue_name)
except:
log += "Could not store result, most likely failed during Omega step!\n"
success_status = False
oehandler.Clear()
# Clean up
ifs_sdf.close()
ifs_mol2.close()
# Write state penalties.
outfile = open(name + '-state-penalties.out', 'w')
for (index, charged_molecule) in enumerate(charged_molecules):
# Get Epik data.
log += "Writing Epik data for state {:d}\n".format(index + 1)
epik_Ionization_Penalty = float(
oechem.OEGetSDData(charged_molecule, "r_epik_Ionization_Penalty"))
epik_Ionization_Penalty_Charging = float(
oechem.OEGetSDData(charged_molecule,
"r_epik_Ionization_Penalty_Charging"))
epik_Ionization_Penalty_Neutral = float(
oechem.OEGetSDData(charged_molecule,
"r_epik_Ionization_Penalty_Neutral"))
epik_State_Penalty = float(
oechem.OEGetSDData(charged_molecule, "r_epik_State_Penalty"))
epik_Tot_Q = int(oechem.OEGetSDData(charged_molecule, "i_epik_Tot_Q"))
outfile.write('%16.8f\n' % epik_State_Penalty)
outfile.close()
# Write as PDB
charged_pdb_filename = name + '-charged_output.pdb'
ofs = oechem.oemolostream(charged_pdb_filename)
flavor = oechem.OEOFlavor_PDB_CurrentResidues | oechem.OEOFlavor_PDB_ELEMENT | oechem.OEOFlavor_PDB_BONDS | oechem.OEOFlavor_PDB_HETBONDS | oechem.OEOFlavor_PDB_BOTH
ofs.SetFlavor(oechem.OEFormat_PDB, flavor)
for (index, charged_molecule) in enumerate(charged_molecules):
# Fix residue names
for atom in charged_molecule.GetAtoms():
residue = oechem.OEAtomGetResidue(atom)
residue.SetName(residue_name)
oechem.OEAtomSetResidue(atom, residue)
oechem.OEWriteMolecule(ofs, charged_molecule)
ofs.close()
# Write molecules as mol2.
charged_mol2_filename = name + '-charged_output.mol2'
write_mol2_preserving_atomnames(charged_mol2_filename, charged_molecules,
residue_name)
log += "Run completed.\n"
if success_status:
log += "Status: Success\n"
else:
log += "Status: Failure\n"
log += "Failed states: {}\n".format(" ".join(
[str(state) for state in sorted(list(failed_states))]))
with open("log.txt", 'w') as logfile:
logfile.write(log)
return log, success_status
def pack_box(molecules,
n_copies,
tolerance=2.0,
box_size=None,
mass_density=None,
verbose=False):
"""Run packmol to generate a box containing a mixture of molecules.
Parameters
----------
molecules : list of OEMol
Molecules in the system (with 3D geometries)
n_copies : list of int (same length as 'molecules')
Number of copies of the molecules
tolerance : float, optional, default=2.0
The mininum spacing between molecules during packing. In ANGSTROMS!
box_size : simtk.unit.Quantity in units compatible with angstroms
The size of the box to generate.
Default generates boxes that are very large for increased stability.
May require extra time for energy minimization and equilibration.
mass_density : simtk.unit.Quantity with units compatible with grams/milliliters, optional, default = 1.0*grams/milliliters
Target mass density for final system, if available.
verbose : bool, optional, default=False
If True, verbose output is written.
Returns
-------
topology : simtk.openmm.Topology
Topology of the resulting system
positions : simtk.unit.Quantity wrapped [natoms,3] numpy array with units compatible with angstroms
Single frame trajectory with mixture box.
"""
assert len(molecules) == len(
n_copies), "Length of 'molecules' and 'n_copies' must be identical"
# Create PDB files for all components
pdb_filenames = list()
pdb_flavor = oechem.OEOFlavor_PDB_CurrentResidues | oechem.OEOFlavor_PDB_ELEMENT | oechem.OEOFlavor_PDB_BONDS | oechem.OEOFlavor_PDB_HETBONDS | oechem.OEOFlavor_PDB_BOTH
for molecule in molecules:
tmp_filename = tempfile.mktemp(suffix=".pdb")
pdb_filenames.append(tmp_filename)
# Write PDB file
mol_copy = copy.deepcopy(molecule)
ofs = oechem.oemolostream(tmp_filename)
ofs.SetFlavor(oechem.OEFormat_PDB, pdb_flavor)
# Fix residue names
residue_name = "".join(
[random.choice(string.ascii_uppercase) for i in range(3)])
for atom in mol_copy.GetAtoms():
residue = oechem.OEAtomGetResidue(atom)
residue.SetName(residue_name)
oechem.OEAtomSetResidue(atom, residue)
oechem.OEWriteMolecule(ofs, mol_copy)
ofs.close()
# Run packmol
PACKMOL_PATH = find_executable("packmol")
if PACKMOL_PATH is None:
raise (IOError("Packmol not found, cannot run pack_box()"))
output_filename = tempfile.mktemp(suffix=".pdb")
# Approximate volume to initialize box
if (box_size is None):
if (mass_density is not None):
# Estimate box_size from mass density.
box_size = approximate_volume_by_density(molecules,
n_copies,
mass_density=mass_density)
else:
# Use vdW radii to estimate box_size
box_size = approximate_volume(molecules, n_copies)
header = HEADER_TEMPLATE % (tolerance, output_filename)
for (pdb_filename, molecule, count) in zip(pdb_filenames, molecules,
n_copies):
header = header + BOX_TEMPLATE % (
pdb_filename, count, box_size / unit.angstroms,
box_size / unit.angstroms, box_size / unit.angstroms)
pwd = os.getcwd()
if verbose: print(header)
# Write packmol input
packmol_filename = "packmol_input.txt"
packmol_filename = tempfile.mktemp(suffix=".txt")
file_handle = open(packmol_filename, 'w')
file_handle.write(header)
file_handle.close()
os.system("%s < %s" % (PACKMOL_PATH, packmol_filename))
# Read the resulting PDB file.
pdbfile = app.PDBFile(output_filename)
# Extract topology and positions
topology = pdbfile.getTopology()
positions = pdbfile.getPositions()
return [topology, positions]
def oesolvate(solute,
density=1.0,
padding_distance=10.0,
distance_between_atoms=2.5,
solvents='tip3p',
molar_fractions='1.0',
geometry='box',
close_solvent=True,
salt='[Na+], [Cl-]',
salt_concentration=0.0,
neutralize_solute=True,
verbose=False,
return_components=False,
**kargs):
"""
This function solvates the passed solute in a cubic box or a sphere by using Packmol. Packmol
creates an initial point for molecular dynamics simulations by packing molecule in defined regions
of space. For additional info:
http://www.ime.unicamp.br/~martinez/packmol/home.shtml
The geometry volume is estimated by the using the padding parameter and the solute size.
The number of solvent molecules is calculated by using the specified density and volume.
Solvent molecules are specified as comma separated smiles strings. The molar fractions
of each solvent molecule are specified in a similar fashion. By default if the solute is
charged counter ions are added to neutralize it
Parameters:
-----------
solute: OEMol molecule
The solute to solvate
density: float
The solution density in g/ml
padding_distance: float
The largest dimension of the solute (along the x, y, or z axis) is determined (in A),
and a cubic box of size (largest dimension)+2*padding is used
distance_between_atoms: float
The minimum distance between atoms in A
solvents: python string
A comma separated smiles string or keywords for the solvent molecules.
Special water models can be selected by using the keywords:
tip3p for TIP3P water model geometry
molar_fractions: python string
A comma separated molar fraction string of the solvent molecules
close_solvent: boolean
If True solvent molecules will be placed very close to the solute
salt: python string
A comma separated string of the dissociated salt in solution
salt_concentration: float
Salt concentration in millimolar
neutralize_solute: boolean
If True counter-ions will be added to the solution to neutralize the solute
verbose: Bool
If True verbose mode is enabled
return_components: Bool
If True the added solvent molecules are also returned as OEMol
Return:
-------
oe_mol: OEMol
The solvated system. If the selected geometry is a box a SD tag with
name 'box_vector' is attached the output molecule containing
the system box vectors.
oe_mol_components: OEMol
If the return_components flag is True the added solvent molecules are
returned as an additional OEMol
"""
def BoundingBox(molecule):
"""
This function calculates the Bounding Box of the passed
molecule
molecule: OEMol
return: bb (numpy array)
the calculated bounding box is returned as numpy array:
[(xmin,ymin,zmin), (xmax,ymax,zmax)]
"""
coords = [v for k, v in molecule.GetCoords().items()]
np_coords = np.array(coords)
min_coord = np_coords.min(axis=0)
max_coord = np_coords.max(axis=0)
bb = np.array([min_coord, max_coord])
return bb
if shutil.which("packmol") is None:
raise (IOError("Packmol executable not found"))
# Extract solvent smiles strings and mole fractions
solvents = [sm.strip() for sm in solvents.split(',')]
fractions = [float(mf) for mf in molar_fractions.split(',')]
# If the smiles string and mole fractions lists have different lengths raise an error
if len(solvents) != len(fractions):
raise ValueError(
"Selected solvent number and selected molar fraction number mismatch: {} vs {}"
.format(len(solvents), len(fractions)))
# Remove smiles string with 0.0 mole fraction
solvent_smiles = [
solvents[i] for i, v in enumerate(fractions) if fractions[i]
]
mol_fractions = [mf for mf in fractions if mf]
# Mole fractions are non-negative numbers
if any([v < 0.0 for v in mol_fractions]):
raise ValueError("Error: Mole fractions are non-negative real numbers")
# Mole fractions must sum up to 1.0
if abs(sum(mol_fractions) - 1.0) > 0.001:
oechem.OEThrow.Error("Error: Mole fractions do not sum up to 1.0")
if geometry not in ['box', 'sphere']:
raise ValueError(
"Error geometry: the supported geometries are box and sphere not {}"
.format(geometry))
# Set Units
density = density * unit.grams / unit.milliliter
padding_distance = padding_distance * unit.angstrom
salt_concentration = salt_concentration * unit.millimolar
# Calculate the Solute Bounding Box
BB_solute = BoundingBox(solute)
# Estimate of the box cube length
box_edge = 2.0 * padding_distance + np.max(BB_solute[1] -
BB_solute[0]) * unit.angstrom
if geometry == 'box':
# Box Volume
Volume = box_edge**3
if geometry == 'sphere':
Volume = (4.0 / 3.0) * 3.14159265 * (0.5 * box_edge)**3
# Omega engine is used to generate conformations
omegaOpts = oeomega.OEOmegaOptions()
omegaOpts.SetMaxConfs(1)
omegaOpts.SetStrictStereo(False)
omega = oeomega.OEOmega(omegaOpts)
# Create a string code to identify the solute residues. The code ID used is based
# on the residue number id, the residue name and the chain id:
# id+resname+chainID
hv_solute = oechem.OEHierView(
solute,
oechem.OEAssumption_BondedResidue + oechem.OEAssumption_ResPerceived)
solute_resid_list = []
for chain in hv_solute.GetChains():
for frag in chain.GetFragments():
for hres in frag.GetResidues():
oe_res = hres.GetOEResidue()
solute_resid_list.append(
str(oe_res.GetResidueNumber()) + oe_res.GetName() +
chain.GetChainID())
# Solvent component list_names
solvent_resid_dic_names = dict()
# Neutralize solute
ion_sum_wgt_n_ions = 0.0 * unit.grams / unit.mole
if neutralize_solute:
# Container for the counter-ions
oe_ions = []
# Container for the ion smiles strings
ions_smiles = []
solute_formal_charge = 0
for at in solute.GetAtoms():
solute_formal_charge += at.GetFormalCharge()
if solute_formal_charge > 0:
ions_smiles.append("[Cl-]")
elif solute_formal_charge < 0:
ions_smiles.append("[Na+]")
else:
pass
# Total number of counter-ions to neutralize the solute
n_ions = abs(solute_formal_charge)
# print("Counter ions to add = {} of {}".format(n_ions, ions_smiles[0]))
# Ions
if n_ions >= 1:
for sm in ions_smiles:
mol = oechem.OEMol()
if not oechem.OESmilesToMol(mol, sm):
raise ValueError(
"Error counter ions: SMILES string parsing fails for the string: {}"
.format(sm))
# Generate conformer
if not omega(mol):
raise ValueError(
"Error counter ions: Conformer generation fails for the molecule with "
"smiles string: {}".format(sm))
oe_ions.append(mol)
if sm == '[Na+]':
solvent_resid_dic_names[' NA'] = mol
else:
solvent_resid_dic_names[' CL'] = mol
ion_sum_wgt = 0.0 * unit.grams / unit.mole
for ion in oe_ions:
# Molecular weight
ion_sum_wgt += oechem.OECalculateMolecularWeight(
ion) * unit.grams / unit.mole
ion_sum_wgt_n_ions = ion_sum_wgt * n_ions
# Create ions .pdb files
ions_smiles_pdbs = []
for i in range(0, len(ions_smiles)):
pdb_name = os.path.basename(tempfile.mktemp(suffix='.pdb'))
pdb_name = ions_smiles[i] + '_' + pdb_name
ions_smiles_pdbs.append(pdb_name)
for i in range(0, len(ions_smiles)):
ofs = oechem.oemolostream(ions_smiles_pdbs[i])
oechem.OEWriteConstMolecule(ofs, oe_ions[i])
# Add salts to the solution
# Solvent smiles string parsing
char_set = string.ascii_uppercase
salt_sum_wgt_n_salt = 0.0 * unit.grams / unit.mole
if salt_concentration > 0.0 * unit.millimolar:
salt_smiles = [sm.strip() for sm in salt.split(',')]
# Container list of oemol salt molecules generated by using smiles strings
oe_salt = []
for sm in salt_smiles:
mol_salt = oechem.OEMol()
if not oechem.OESmilesToMol(mol_salt, sm):
raise ValueError(
"Error salt: SMILES string parsing fails for the string: {}"
.format(sm))
# Generate conformer
if not omega(mol_salt):
raise ValueError(
"Error salt: Conformer generation fails for the "
"molecule with smiles string: {}".format(sm))
# Unique 3 code letter are set as solvent residue names
solv_id = ''.join(random.sample(char_set * 3, 3))
# Try to recognize the residue name
oechem.OEPerceiveResidues(mol_salt)
for atmol in mol_salt.GetAtoms():
res = oechem.OEAtomGetResidue(atmol)
if res.GetName() == 'UNL':
res.SetName(solv_id)
oechem.OEAtomSetResidue(atmol, res)
if solv_id not in solvent_resid_dic_names:
solvent_resid_dic_names[solv_id] = mol_salt
else:
if res.GetName() not in solvent_resid_dic_names:
solvent_resid_dic_names[res.GetName()] = mol_salt
break
oe_salt.append(mol_salt)
n_salt = int(
round(unit.AVOGADRO_CONSTANT_NA * salt_concentration *
Volume.in_units_of(unit.liter)))
# for i in range(0, len(salt_smiles)):
# print("Number of molecules for the salt component {} = {}".format(salt_smiles[i], n_salt))
salt_sum_wgt = 0.0 * unit.grams / unit.mole
for salt in oe_salt:
# Molecular weight
salt_sum_wgt += oechem.OECalculateMolecularWeight(
salt) * unit.grams / unit.mole
salt_sum_wgt_n_salt = salt_sum_wgt * n_salt
# Create salt .pdb files
if n_salt >= 1:
salt_pdbs = []
for i in range(0, len(salt_smiles)):
pdb_name = os.path.basename(tempfile.mktemp(suffix='.pdb'))
# pdb_name = salt_smiles[i] + '_' + pdb_name
salt_pdbs.append(pdb_name)
for i in range(0, len(salt_smiles)):
ofs = oechem.oemolostream(salt_pdbs[i])
oechem.OEWriteConstMolecule(ofs, oe_salt[i])
# Container list of oemol solvent molecules generated by using smiles strings
oe_solvents = []
for sm in solvent_smiles:
if sm == 'tip3p':
tip3p_fn = os.path.join(PACKAGE_DIR, 'oeommtools', 'data',
'tip3p.pdb')
ifs = oechem.oemolistream(tip3p_fn)
mol_sol = oechem.OEMol()
if not oechem.OEReadMolecule(ifs, mol_sol):
raise IOError(
"It was not possible to read the tip3p molecule file")
else:
mol_sol = oechem.OEMol()
if not oechem.OESmilesToMol(mol_sol, sm):
raise ValueError(
"Error solvent: SMILES string parsing fails for the string: {}"
.format(sm))
# Generate conformer
if not omega(mol_sol):
raise ValueError(
"Error solvent: Conformer generation fails for "
"the molecule with smiles string: {}".format(sm))
# Unique 3 code letter are set as solvent residue names
solv_id = ''.join(random.sample(char_set * 3, 3))
# Try to recognize the residue name
oechem.OEPerceiveResidues(mol_sol)
for atmol in mol_sol.GetAtoms():
res = oechem.OEAtomGetResidue(atmol)
if res.GetName() == 'UNL':
res.SetName(solv_id)
oechem.OEAtomSetResidue(atmol, res)
if solv_id not in solvent_resid_dic_names:
solvent_resid_dic_names[solv_id] = mol_sol
else:
if res.GetName() not in solvent_resid_dic_names:
solvent_resid_dic_names[res.GetName()] = mol_sol
break
oe_solvents.append(mol_sol)
# Sum of the solvent molecular weights
solvent_sum_wgt_frac = 0.0 * unit.grams / unit.mole
for idx in range(0, len(oe_solvents)):
# Molecular weight
wgt = oechem.OECalculateMolecularWeight(
oe_solvents[idx]) * unit.grams / unit.mole
solvent_sum_wgt_frac += wgt * mol_fractions[idx]
# Solute molecular weight
solute_wgt = oechem.OECalculateMolecularWeight(
solute) * unit.gram / unit.mole
# Estimate of the number of each molecular species present in the solution accordingly
# to their molar fraction fi:
#
# ni = fi*(density*volume*NA - wgt_solute - sum_k(wgt_salt_k*nk) - wgt_ion*n_ion)/sum_j(wgt_nj * fj)
#
# where ni is the number of molecule of specie i, density the mixture density, volume the
# mixture volume, wgt_solute the molecular weight of the solute, wgt_salt_k the molecular
# weight of the salt component k, nk the number of molecule of salt component k, wgt_ion
# the counter ion molecular weight, n_ions the number of counter ions and wgt_nj the molecular
# weight of the molecule specie j with molar fraction fj
div = (unit.AVOGADRO_CONSTANT_NA * density * Volume -
(solute_wgt + salt_sum_wgt_n_salt +
ion_sum_wgt_n_ions)) / solvent_sum_wgt_frac
# Solvent number of monomers
n_monomers = [int(round(mf * div)) for mf in mol_fractions]
if not all([nm > 0 for nm in n_monomers]):
raise ValueError(
"Error negative number of solvent components: the density could be too low"
)
# for i in range(0, len(solvent_smiles)):
# print("Number of molecules for the component {} = {}".format(solvent_smiles[i], n_monomers[i]))
# Packmol Configuration file setting
if close_solvent:
header_template = """\n# Mixture\ntolerance {}\nfiletype pdb\noutput {}\nadd_amber_ter\navoid_overlap no"""
else:
header_template = """\n# Mixture\ntolerance {}\nfiletype pdb\noutput {}\nadd_amber_ter\navoid_overlap yes"""
# Templates strings
solute_template = """\n\n# Solute\nstructure {}\nnumber 1\nfixed 0. 0. 0. 0. 0. 0.\nresnumbers 1\nend structure"""
if geometry == 'box':
solvent_template = """\nstructure {}\nnumber {}\ninside box {:0.3f} {:0.3f} {:0.3f} {:0.3f} {:0.3f} {:0.3f}\
\nchain !\nresnumbers 3\nend structure"""
if geometry == 'sphere':
solvent_template = """\nstructure {}\nnumber {}\ninside sphere {:0.3f} {:0.3f} {:0.3f} {:0.3f}\
\nchain !\nresnumbers 3\nend structure"""
# Create solvents .pdb files
solvent_pdbs = []
for i in range(0, len(solvent_smiles)):
pdb_name = os.path.basename(tempfile.mktemp(suffix='.pdb'))
solvent_pdbs.append(pdb_name)
for i in range(0, len(solvent_smiles)):
ofs = oechem.oemolostream(solvent_pdbs[i])
oechem.OEWriteConstMolecule(ofs, oe_solvents[i])
solute_pdb = 'solute' + '_' + os.path.basename(
tempfile.mktemp(suffix='.pdb'))
ofs = oechem.oemolostream(solute_pdb)
if solute.GetMaxConfIdx() > 1:
raise ValueError("Solutes with multiple conformers are not supported")
else:
oechem.OEWriteConstMolecule(ofs, solute)
# Write Packmol header section
mixture_pdb = 'mixture' + '_' + os.path.basename(
tempfile.mktemp(suffix='.pdb'))
body = header_template.format(distance_between_atoms, mixture_pdb)
# Write Packmol configuration file solute section
body += solute_template.format(solute_pdb)
# The solute is centered inside the box
xc = (BB_solute[0][0] + BB_solute[1][0]) / 2.
yc = (BB_solute[0][1] + BB_solute[1][1]) / 2.
zc = (BB_solute[0][2] + BB_solute[1][2]) / 2.
# Correct for periodic box conditions to avoid
# steric clashes at the box edges
pbc_correction = 1.0 * unit.angstrom
xmin = xc - ((box_edge - pbc_correction) / 2.) / unit.angstrom
xmax = xc + ((box_edge - pbc_correction) / 2.) / unit.angstrom
ymin = yc - ((box_edge - pbc_correction) / 2.) / unit.angstrom
ymax = yc + ((box_edge - pbc_correction) / 2.) / unit.angstrom
zmin = zc - ((box_edge - pbc_correction) / 2.) / unit.angstrom
zmax = zc + ((box_edge - pbc_correction) / 2.) / unit.angstrom
# Packmol setting for the solvent section
body += '\n\n# Solvent'
for i in range(0, len(solvent_smiles)):
if geometry == 'box':
body += solvent_template.format(solvent_pdbs[i], n_monomers[i],
xmin, ymin, zmin, xmax, ymax, zmax)
if geometry == 'sphere':
body += solvent_template.format(solvent_pdbs[i], n_monomers[i], xc,
yc, zc,
0.5 * box_edge / unit.angstrom)
# Packmol setting for the salt section
if salt_concentration > 0.0 * unit.millimolar and n_salt >= 1:
body += '\n\n# Salt'
for i in range(0, len(salt_smiles)):
if geometry == 'box':
body += solvent_template.format(salt_pdbs[i],
int(round(n_salt)), xmin, ymin,
zmin, xmax, ymax, zmax)
if geometry == 'sphere':
body += solvent_template.format(salt_pdbs[i],
int(round(n_salt)), xc, yc, zc,
0.5 * box_edge / unit.angstrom)
# Packmol setting for the ions section
if neutralize_solute and n_ions >= 1:
body += '\n\n# Counter Ions'
for i in range(0, len(ions_smiles)):
if geometry == 'box':
body += solvent_template.format(ions_smiles_pdbs[i], n_ions,
xmin, ymin, zmin, xmax, ymax,
zmax)
if geometry == 'sphere':
body += solvent_template.format(ions_smiles_pdbs[i], n_ions,
xc, yc, zc,
0.5 * box_edge / unit.angstrom)
# Packmol configuration file
packmol_filename = os.path.basename(tempfile.mktemp(suffix='.inp'))
with open(packmol_filename, 'w') as file_handle:
file_handle.write(body)
# Call Packmol
if not verbose:
mute_output = open(os.devnull, 'w')
with open(packmol_filename, 'r') as file_handle:
subprocess.check_call(['packmol'],
stdin=file_handle,
stdout=mute_output,
stderr=mute_output)
else:
with open(packmol_filename, 'r') as file_handle:
subprocess.check_call(['packmol'], stdin=file_handle)
# Read in the Packmol solvated system
solvated = oechem.OEMol()
if os.path.exists(mixture_pdb + '_FORCED'):
os.rename(mixture_pdb + '_FORCED', mixture_pdb)
print("Warning: Packing solution is not optimal")
ifs = oechem.oemolistream(mixture_pdb)
oechem.OEReadMolecule(ifs, solvated)
# To avoid to change the user oemol starting solute by reading in
# the generated mixture pdb file and loosing molecule info, the
# solvent molecules are extracted from the mixture system and
# added back to the starting solute
# Extract from the solution system the solvent molecules
# by checking the previous solute generated ID: id+resname+chainID
hv_solvated = oechem.OEHierView(
solvated,
oechem.OEAssumption_BondedResidue + oechem.OEAssumption_ResPerceived)
# This molecule will hold the solvent molecules generated directly from
# the omega conformers. This is useful to avoid problems related to read in
# the solvent molecules from pdb files and triggering unwanted perceiving actions
new_components = oechem.OEMol()
bv = oechem.OEBitVector(solvated.GetMaxAtomIdx())
for chain in hv_solvated.GetChains():
for frag in chain.GetFragments():
for hres in frag.GetResidues():
oe_res = hres.GetOEResidue()
if str(oe_res.GetResidueNumber()) + oe_res.GetName(
) + chain.GetChainID() not in solute_resid_list:
oechem.OEAddMols(new_components,
solvent_resid_dic_names[oe_res.GetName()])
atms = hres.GetAtoms()
for at in atms:
bv.SetBitOn(at.GetIdx())
pred = oechem.OEAtomIdxSelected(bv)
components = oechem.OEMol()
oechem.OESubsetMol(components, solvated, pred)
new_components.SetCoords(components.GetCoords())
# This is necessary otherwise just one big residue is created
oechem.OEPerceiveResidues(new_components)
# Add the solvent molecules to the solute copy
solvated_system = solute.CreateCopy()
oechem.OEAddMols(solvated_system, new_components)
# Set Title
solvated_system.SetTitle(solute.GetTitle())
# Set ions resname to Na+ and Cl-
for at in solvated_system.GetAtoms():
res = oechem.OEAtomGetResidue(at)
if res.GetName() == ' NA':
res.SetName("Na+")
oechem.OEAtomSetResidue(atmol, res)
elif res.GetName() == ' CL':
res.SetName("Cl-")
oechem.OEAtomSetResidue(atmol, res)
else:
pass
# Cleaning
to_delete = solvent_pdbs + [packmol_filename, solute_pdb, mixture_pdb]
if salt_concentration > 0.0 * unit.millimolar and n_salt >= 1:
to_delete += salt_pdbs
if neutralize_solute and n_ions >= 1:
to_delete += ions_smiles_pdbs
for fn in to_delete:
try:
os.remove(fn)
except:
pass
# Calculate the solution total density
total_wgt = oechem.OECalculateMolecularWeight(
solvated_system) * unit.gram / unit.mole
density_mix = (1 / unit.AVOGADRO_CONSTANT_NA) * total_wgt / Volume
print("Computed Solution Density = {}".format(
density_mix.in_units_of(unit.gram / unit.milliliter)))
# Threshold checking
ths = 0.1 * unit.gram / unit.milliliter
if not abs(density -
density_mix.in_units_of(unit.gram / unit.milliliter)) < ths:
raise ValueError(
"Error: the computed density for the solute {} does not match the selected density {} vs {}"
.format(solute.GetTitle(), density_mix, density))
if geometry == 'box':
# Define the box vector and attached it as SD tag to the solvated system
# with ID tag: 'box_vectors'
box_vectors = (Vec3(box_edge / unit.angstrom, 0.0,
0.0), Vec3(0.0, box_edge / unit.angstrom, 0.0),
Vec3(0.0, 0.0,
box_edge / unit.angstrom)) * unit.angstrom
box_vectors = data_utils.encodePyObj(box_vectors)
solvated_system.SetData(oechem.OEGetTag('box_vectors'), box_vectors)
if return_components:
new_components.SetTitle(solute.GetTitle() + '_solvent_comp')
return solvated_system, new_components
else:
return solvated_system