def test_atom_map(self):
"""Test get atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_1 = openeye.smiles_to_oemol('CC[N+]#C')
inf = get_fn('ethylmethylidyneamonium.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i+1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping-1))
atom_2.SetAtomicNum(i+1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1), oechem.OECreateCanSmiString(mol_2))
# Test aromatic molecule
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = openeye.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i+1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping-1))
atom_2.SetAtomicNum(i+1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1), oechem.OECreateCanSmiString(mol_2))
def SmilesToFragments(smiles, fgroup_smarts, bondOrderThreshold=1.2, chargesMol=True):
"""
Fragment molecule at bonds below Bond Order Threshold
Parameters
----------
smiles: str
smiles string of molecule to fragment
Returns
-------
frags: list of OE AtomBondSets
"""
# Charge molecule
mol = oechem.OEGraphMol()
oemol = openeye.smiles_to_oemol(smiles)
charged = openeye.get_charges(oemol, keep_confs=1)
# Tag functional groups
_tag_fgroups(charged, fgroups_smarts=fgroup_smarts)
# Generate fragments
G = OeMolToGraph(charged)
subraphs = FragGraph(G, bondOrderThreshold=bondOrderThreshold)
frags = []
for subraph in subraphs:
frags.append(subgraphToAtomBondSet(G, subraph, charged))
if chargesMol:
return frags, charged
else:
return frags
def enumerate_conformations(name, smiles):
"""Generate geometry and run epik."""
# Generate molecule geometry with OpenEye
print "Generating molecule {}".format(name)
oe_molecule = openeye.smiles_to_oemol(smiles)
try:
oe_molecule = openeye.get_charges(oe_molecule, keep_confs=1)
except RuntimeError as e:
traceback.print_exc()
print "Skipping molecule " + name
return
# 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)
# Save mol2 file with residue name = first three uppercase letters
print "Running epik on molecule {}".format(name)
mol2_file_path = output_basepath + '-input.mol2'
residue_name = re.sub('[^A-Za-z]+', '', name.upper())[:3]
openeye.molecule_to_mol2(oe_molecule, mol2_file_path, residue_name=residue_name)
# Run epik on mol2 file
mae_file_path = output_basepath + '-epik.mae'
schrodinger.run_epik(mol2_file_path, mae_file_path, tautomerize=True,
max_structures=32, ph_tolerance=10.0)
# Convert maestro file to sdf and mol2
schrodinger.run_structconvert(mae_file_path, output_basepath + '-epik.sdf')
schrodinger.run_structconvert(mae_file_path, output_basepath + '-epik.mol2')
def test_atom_map_order(self):
"""Test atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_from_tagged_smiles = openeye.smiles_to_oemol(tagged_smiles)
atom_map = utils.get_atom_map(tagged_smiles, mol_from_tagged_smiles)
# Compare atom map to tag
for i in range(1, len(atom_map) +1):
atom_1 = mol_from_tagged_smiles.GetAtom(oechem.OEHasAtomIdx(atom_map[i]))
self.assertEqual(i, atom_1.GetMapIdx())
def test_atom_map_order(self):
"""Test atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_from_tagged_smiles = openeye.smiles_to_oemol(tagged_smiles)
atom_map = utils.get_atom_map(tagged_smiles, mol_from_tagged_smiles)
# Compare atom map to tag
for i in range(1, len(atom_map) + 1):
atom_1 = mol_from_tagged_smiles.GetAtom(
oechem.OEHasAtomIdx(atom_map[i]))
self.assertEqual(i, atom_1.GetMapIdx())
def test_atom_map(self):
"""Test get atom map"""
from openeye import oechem
tagged_smiles = '[H:5][C:1]#[N+:4][C:3]([H:9])([H:10])[C:2]([H:6])([H:7])[H:8]'
mol_1 = openeye.smiles_to_oemol('CC[N+]#C')
inf = get_fn('ethylmethylidyneamonium.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1),
oechem.OECreateCanSmiString(mol_2))
# Test aromatic molecule
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = openeye.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
self.assertEqual(oechem.OECreateCanSmiString(mol_1),
oechem.OECreateCanSmiString(mol_2))
def get_atom_map(tagged_smiles, molecule=None):
"""
Returns a dictionary that maps tag on SMILES to atom index in molecule.
Parameters
----------
tagged_smiles: str
index-tagged explicit hydrogen SMILES string
molecule: OEMol
molecule to generate map for. If None, a new OEMol will be generated from the tagged SMILES, the map will map to
this molecule and it will be returned.
Returns
-------
atom_map: dict
a dictionary that maps tag to atom index {tag:idx}
molecule: OEMol
If a molecule was not provided, the generated molecule will be returned.
"""
if molecule is None:
molecule = openeye.smiles_to_oemol(tagged_smiles)
ss = oechem.OESubSearch(tagged_smiles)
oechem.OEPrepareSearch(molecule, ss)
ss.SetMaxMatches(1)
atom_map = {}
t1 = time.time()
matches = [m for m in ss.Match(molecule)]
t2 = time.time()
seconds = t2 - t1
logger().info("Substructure search took {} seconds".format(seconds))
if not matches:
logger().info("MCSS failed for {}, smiles: {}".format(
molecule.GetTitle(), tagged_smiles))
return False
for match in matches:
for ma in match.GetAtoms():
atom_map[ma.pattern.GetMapIdx()] = ma.target.GetIdx()
# sanity check
mol = oechem.OEGraphMol()
oechem.OESubsetMol(mol, match, True)
logger().info("Match SMILES: {}".format(oechem.OEMolToSmiles(mol)))
if molecule is None:
return molecule, atom_map
return atom_map
def get_atom_map(tagged_smiles, molecule=None):
"""
Returns a dictionary that maps tag on SMILES to atom index in molecule.
Parameters
----------
tagged_smiles: str
index-tagged explicit hydrogen SMILES string
molecule: OEMol
molecule to generate map for. If None, a new OEMol will be generated from the tagged SMILES, the map will map to
this molecule and it will be returned.
Returns
-------
atom_map: dict
a dictionary that maps tag to atom index {tag:idx}
molecule: OEMol
If a molecule was not provided, the generated molecule will be returned.
"""
if molecule is None:
molecule = openeye.smiles_to_oemol(tagged_smiles)
ss = oechem.OESubSearch(tagged_smiles)
oechem.OEPrepareSearch(molecule, ss)
ss.SetMaxMatches(1)
atom_map = {}
t1 = time.time()
matches = [m for m in ss.Match(molecule)]
t2 = time.time()
seconds = t2-t1
logger().info("Substructure search took {} seconds".format(seconds))
if not matches:
logger().info("MCSS failed for {}, smiles: {}".format(molecule.GetTitle(), tagged_smiles))
return False
for match in matches:
for ma in match.GetAtoms():
atom_map[ma.pattern.GetMapIdx()] = ma.target.GetIdx()
# sanity check
mol = oechem.OEGraphMol()
oechem.OESubsetMol(mol, match, True)
logger().info("Match SMILES: {}".format(oechem.OEMolToSmiles(mol)))
if molecule is None:
return molecule, atom_map
return atom_map
def __init__(self, cas_or_aa, min_atoms=6):
"""
Initialize using cas numbers OR amino acid name
Requires openmoltools.openeye and cirpy
Arguments
cas_or_aa (list of strings) either cas number or name of amino acid
Optional Arguments
min_atoms (int) - a minimum number of atoms for substructure match (default: 6)
Creates class variables:
self.cas_or_aa (list of strings)
input representing molecules to be combined
self.smiles_strings (list of strings)
smiles representation of molecules to be combined
self.ligands (list of OEMol)
openeye molecule representation of molecules to be combined
self.title (string)
used as an identifier for input group of molecules
self.min_atoms (int)
minimum number of common atoms to constitute a substructure match (default: 6)
"""
self.cas_or_aa = cas_or_aa
self.smiles_strings = []
self.ligands = []
for cas in cas_or_aa:
smiles = cirpy.resolve(cas, 'smiles')
self.smiles_strings.append(smiles)
ligand = openeye.smiles_to_oemol(smiles)
ligand = openeye.get_charges(ligand, strictStereo=False)
self.ligands.append(ligand)
self.title = self.cas_or_aa[0] + "_and_analogs"
self.min_atoms = min_atoms
self.common_substructure = None
self.dual_topology = None
self.each_molecule_N = []
self.mapping_dictionaries = []
self.pdb_filename = None
self.ffxml_filename = None
def __init__(self, cas_or_aa, min_atoms=6):
"""
Initialize using cas numbers OR amino acid name
Requires openmoltools.openeye and cirpy
Arguments
cas_or_aa (list of strings) either cas number or name of amino acid
Optional Arguments
min_atoms (int) - a minimum number of atoms for substructure match (default: 6)
Creates class variables:
self.cas_or_aa (list of strings)
input representing molecules to be combined
self.smiles_strings (list of strings)
smiles representation of molecules to be combined
self.ligands (list of OEMol)
openeye molecule representation of molecules to be combined
self.title (string)
used as an identifier for input group of molecules
self.min_atoms (int)
minimum number of common atoms to constitute a substructure match (default: 6)
"""
self.cas_or_aa = cas_or_aa
self.smiles_strings = []
self.ligands = []
for cas in cas_or_aa:
smiles = cirpy.resolve(cas,'smiles')
self.smiles_strings.append(smiles)
ligand = openeye.smiles_to_oemol(smiles)
ligand = openeye.get_charges(ligand, strictStereo=False)
self.ligands.append(ligand)
self.title = self.cas_or_aa[0]+"_and_analogs"
self.min_atoms = min_atoms
self.common_substructure = None
self.dual_topology = None
self.each_molecule_N = []
self.mapping_dictionaries = []
self.pdb_filename = None
self.ffxml_filename = None
def test_mapped_xyz(self):
"""Test writing out mapped xyz"""
from openeye import oechem, oeomega
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = openeye.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i + 1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping - 1))
atom_2.SetAtomicNum(i + 1)
xyz_1 = utils.to_mapped_xyz(mol_1, atom_map)
# molecule generated from mol2 should be in the right order.
atom_map_mol2 = {
1: 0,
2: 1,
3: 2,
4: 3,
5: 4,
6: 5,
7: 6,
8: 7,
9: 8,
10: 9,
11: 10,
12: 11,
13: 12,
14: 13,
15: 14
}
xyz_2 = utils.to_mapped_xyz(mol_2, atom_map_mol2)
for ele1, ele2 in zip(xyz_1.split('\n')[:-1], xyz_2.split('\n')[:-1]):
self.assertEqual(ele1.split(' ')[2], ele2.split(' ')[2])
def SmilesToFragments(smiles,
fgroup_smarts,
bondOrderThreshold=1.2,
chargesMol=True):
"""
Fragment molecule at bonds below Bond Order Threshold
Parameters
----------
smiles: str
smiles string of molecule to fragment
Returns
-------
frags: list of OE AtomBondSets
"""
# Charge molecule
mol = oechem.OEGraphMol()
oemol = openeye.smiles_to_oemol(smiles)
charged = openeye.get_charges(oemol, keep_confs=1)
# Tag functional groups
_tag_fgroups(charged, fgroups_smarts=fgroup_smarts)
# Generate fragments
G = OeMolToGraph(charged)
subraphs = FragGraph(G, bondOrderThreshold=bondOrderThreshold)
frags = []
for subraph in subraphs:
frags.append(subgraphToAtomBondSet(G, subraph, charged))
if chargesMol:
return frags, charged
else:
return frags
def test_mapped_xyz(self):
"""Test writing out mapped xyz"""
from openeye import oechem, oeomega
tagged_smiles = '[H:10][c:4]1[c:3]([c:2]([c:1]([c:6]([c:5]1[H:11])[H:12])[C:7]([H:13])([H:14])[H:15])[H:8])[H:9]'
mol_1 = openeye.smiles_to_oemol('Cc1ccccc1')
inf = get_fn('toluene.mol2')
ifs = oechem.oemolistream(inf)
mol_2 = oechem.OEMol()
oechem.OEReadMolecule(ifs, mol_2)
atom_map = utils.get_atom_map(tagged_smiles, mol_1)
for i, mapping in enumerate(atom_map):
atom_1 = mol_1.GetAtom(oechem.OEHasAtomIdx(atom_map[mapping]))
atom_1.SetAtomicNum(i+1)
atom_2 = mol_2.GetAtom(oechem.OEHasAtomIdx(mapping-1))
atom_2.SetAtomicNum(i+1)
xyz_1 = utils.to_mapped_xyz(mol_1, atom_map)
# molecule generated from mol2 should be in the right order.
atom_map_mol2 = {1:0, 2:1, 3:2, 4:3, 5:4, 6:5, 7:6, 8:7, 9:8, 10:9, 11:10, 12:11, 13:12, 14:13, 15:14}
xyz_2 = utils.to_mapped_xyz(mol_2, atom_map_mol2)
for ele1, ele2 in zip(xyz_1.split('\n')[:-1], xyz_2.split('\n')[:-1]):
self.assertEqual(ele1.split(' ')[2], ele2.split(' ')[2])
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)
eMolID_can_iso_smiles_dict = eMolID_smiles_dict
pickle.dump(eMolID_can_iso_smiles_dict,
open("eMolID_can_iso_smiles_dict.pickle", "wb"))
print("Finished converting eMolecules SMILES to canonical isomeric SMILES.")
print("\n")
##### CONVERT SMILES TO OEMOL #####
print("Converting SMILES to OEMol...")
eMolID_oemol_dict = {}
for key, value in eMolID_smiles_dict.items():
# Create a OEMolBuilder from a smiles string.
oemol_molecule = omtoe.smiles_to_oemol(smiles=value)
eMolID_oemol_dict[key] = oemol_molecule
# print(oMolID_oemol_dict)
print("\n")
##### GENERATE CHARGED CONFORMERS AND SAVE AS MOL2 FILE #####
mol2_directory_path = "./mol2_files"
if not os.path.exists(mol2_directory_path):
os.makedirs(mol2_directory_path)
print("{} directory created.".format(mol2_directory_path))
print("Generating charged OEMol molecules...")
""" Test fragmentation """
__author__ = 'Chaya D. Stern'
from torsionfit.tests.utils import get_fn, has_openeye, FileIOTestCase
import unittest
# TODO should I move this to SetUp?
if has_openeye:
from openmoltools.openeye import get_charges, smiles_to_oemol
import openeye.oechem as oechem
from torsionfit.qmscan import fragment
mol = smiles_to_oemol(
'CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4'
)
charged = get_charges(mol, keep_confs=1)
class TestFragments(FileIOTestCase):
@unittest.skipUnless(has_openeye, "Cannot test without OpenEye")
def test_tag_funcgroup(self):
""" Test tag functional groups """
tagged_funcgroups = fragment._tag_fgroups(charged)
self.assertEquals(len(tagged_funcgroups), 3)
atom_idx = tagged_funcgroups['amide_0'][0].pop()
atom = charged.GetAtom(oechem.OEHasAtomIdx(atom_idx))
fgroup = atom.GetData('fgroup')
self.assertEquals('amide_0', fgroup)
@unittest.skipUnless(has_openeye, "Cannot test without OpenEye")
def test_tag_rings(self):
# Create output directory
if not os.path.exists(LIGANDS_DIR_PATH):
os.makedirs(LIGANDS_DIR_PATH)
# Parse SMILES file and generate ligand
smiles_file = open(SMILES_FILE_PATH, 'r')
for line in smiles_file:
# Get SMILES representation from CVS file
ligand_name, smiles_str = line.strip().split(',')
print "Generating inhibitor", ligand_name
# Convert to OEMol molecule
mol_oemol = smiles_to_oemol(smiles_str)
mol_oemol.SetTitle(ligand_name)
# Use OpenEye Omega toolkit to generate lowest energy structure
omega = oeomega.OEOmega()
omega.SetCanonOrder(False)
omega.SetMaxConfs(OMEGA_MAX_CONFS)
omega(mol_oemol)
# Generate protonation/tautomeric states with epik and charge molecule
valid_structure = False
with working_directory(temp_dir):
for i in range(mol_oemol.GetMaxConfIdx()):
try:
confomer = mol_oemol.GetConf(oechem.OEHasConfIdx(i))
mk_single_conformer_epik(ligand_name, confomer, pH=PH)
# Create output directory
if not os.path.exists(LIGANDS_DIR_PATH):
os.makedirs(LIGANDS_DIR_PATH)
# Parse SMILES file and generate ligand
smiles_file = open(SMILES_FILE_PATH, 'r')
for line in smiles_file:
# Get SMILES representation from CVS file
ligand_name, smiles_str = line.strip().split(',')
print "Generating inhibitor", ligand_name
# Convert to OEMol molecule
mol_oemol = smiles_to_oemol(smiles_str)
mol_oemol.SetTitle(ligand_name)
# Use OpenEye Omega toolkit to generate lowest energy structure
omega = oeomega.OEOmega()
omega.SetCanonOrder(False)
omega.SetMaxConfs(OMEGA_MAX_CONFS)
omega(mol_oemol)
# Generate protonation/tautomeric states with epik and charge molecule
valid_structure = False
with working_directory(temp_dir):
for i in range(mol_oemol.GetMaxConfIdx()):
try:
confomer = mol_oemol.GetConf(oechem.OEHasConfIdx(i))
mk_single_conformer_epik(ligand_name, confomer, pH=PH)
def __init__(self, molecules: List[str], output_filename: str, ncmc_switching_times: Dict[str, int], equilibrium_steps: Dict[str, int], timestep: unit.Quantity, initial_molecule: str=None, geometry_options: Dict=None):
self._molecules = [SmallMoleculeSetProposalEngine.canonicalize_smiles(molecule) for molecule in molecules]
environments = ['explicit', 'vacuum']
temperature = 298.15 * unit.kelvin
pressure = 1.0 * unit.atmospheres
constraints = app.HBonds
self._storage = NetCDFStorage(output_filename)
self._ncmc_switching_times = ncmc_switching_times
self._n_equilibrium_steps = equilibrium_steps
self._geometry_options = geometry_options
# Create a system generator for our desired forcefields.
from perses.rjmc.topology_proposal import SystemGenerator
system_generators = dict()
from pkg_resources import resource_filename
gaff_xml_filename = resource_filename('perses', 'data/gaff.xml')
barostat = openmm.MonteCarloBarostat(pressure, temperature)
system_generators['explicit'] = SystemGenerator([gaff_xml_filename, 'tip3p.xml'],
forcefield_kwargs={'nonbondedCutoff': 9.0 * unit.angstrom,
'implicitSolvent': None,
'constraints': constraints,
'ewaldErrorTolerance': 1e-5,
'hydrogenMass': 3.0*unit.amu}, periodic_forcefield_kwargs = {'nonbondedMethod': app.PME}
barostat=barostat)
system_generators['vacuum'] = SystemGenerator([gaff_xml_filename],
forcefield_kwargs={'implicitSolvent': None,
'constraints': constraints,
'hydrogenMass': 3.0*unit.amu}, nonperiodic_forcefield_kwargs = {'nonbondedMethod': app.NoCutoff})
#
# Create topologies and positions
#
topologies = dict()
positions = dict()
from openmoltools import forcefield_generators
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(forcefield_generators.gaffTemplateGenerator)
# Create molecule in vacuum.
from perses.utils.openeye import extractPositionsFromOEMol
from openmoltools.openeye import smiles_to_oemol, generate_conformers
if initial_molecule:
smiles = initial_molecule
else:
smiles = np.random.choice(molecules)
molecule = smiles_to_oemol(smiles)
molecule = generate_conformers(molecule, max_confs=1)
topologies['vacuum'] = forcefield_generators.generateTopologyFromOEMol(molecule)
positions['vacuum'] = extractPositionsFromOEMol(molecule)
# Create molecule in solvent.
modeller = app.Modeller(topologies['vacuum'], positions['vacuum'])
modeller.addSolvent(forcefield, model='tip3p', padding=9.0 * unit.angstrom)
topologies['explicit'] = modeller.getTopology()
positions['explicit'] = modeller.getPositions()
# Set up the proposal engines.
proposal_metadata = {}
proposal_engines = dict()
for environment in environments:
proposal_engines[environment] = SmallMoleculeSetProposalEngine(self._molecules,
system_generators[environment])
# Generate systems
systems = dict()
for environment in environments:
systems[environment] = system_generators[environment].build_system(topologies[environment])
# Define thermodynamic state of interest.
thermodynamic_states = dict()
thermodynamic_states['explicit'] = states.ThermodynamicState(system=systems['explicit'],
temperature=temperature, pressure=pressure)
thermodynamic_states['vacuum'] = states.ThermodynamicState(system=systems['vacuum'], temperature=temperature)
# Create SAMS samplers
from perses.samplers.samplers import ExpandedEnsembleSampler, SAMSSampler
mcmc_samplers = dict()
exen_samplers = dict()
sams_samplers = dict()
for environment in environments:
storage = NetCDFStorageView(self._storage, envname=environment)
if self._geometry_options:
n_torsion_divisions = self._geometry_options['n_torsion_divsions'][environment]
use_sterics = self._geometry_options['use_sterics'][environment]
else:
n_torsion_divisions = 180
use_sterics = False
geometry_engine = geometry.FFAllAngleGeometryEngine(storage=storage, n_torsion_divisions=n_torsion_divisions, use_sterics=use_sterics)
move = mcmc.LangevinSplittingDynamicsMove(timestep=timestep, splitting="V R O R V",
n_restart_attempts=10)
chemical_state_key = proposal_engines[environment].compute_state_key(topologies[environment])
if environment == 'explicit':
sampler_state = states.SamplerState(positions=positions[environment],
box_vectors=systems[environment].getDefaultPeriodicBoxVectors())
else:
sampler_state = states.SamplerState(positions=positions[environment])
mcmc_samplers[environment] = mcmc.MCMCSampler(thermodynamic_states[environment], sampler_state, move)
exen_samplers[environment] = ExpandedEnsembleSampler(mcmc_samplers[environment], topologies[environment],
chemical_state_key, proposal_engines[environment],
geometry_engine,
options={'nsteps': self._ncmc_switching_times[environment]}, storage=storage, ncmc_write_interval=self._ncmc_switching_times[environment])
exen_samplers[environment].verbose = True
sams_samplers[environment] = SAMSSampler(exen_samplers[environment], storage=storage)
sams_samplers[environment].verbose = True
# Create test MultiTargetDesign sampler.
from perses.samplers.samplers import MultiTargetDesign
target_samplers = {sams_samplers['explicit']: 1.0, sams_samplers['vacuum']: -1.0}
designer = MultiTargetDesign(target_samplers, storage=self._storage)
# Store things.
self.molecules = molecules
self.environments = environments
self.topologies = topologies
self.positions = positions
self.system_generators = system_generators
self.proposal_engines = proposal_engines
self.thermodynamic_states = thermodynamic_states
self.mcmc_samplers = mcmc_samplers
self.exen_samplers = exen_samplers
self.sams_samplers = sams_samplers
self.designer = designer
def generate_vacuum_hostguest_proposal(current_mol_name="B2",
proposed_mol_name="MOL"):
"""
Generate a test vacuum topology proposal, current positions, and new positions triplet
from two IUPAC molecule names.
Parameters
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
from openmoltools import forcefield_generators
from openmmtools import testsystems
from perses.utils.openeye import smiles_to_oemol
from perses.utils.data import get_data_filename
host_guest = testsystems.HostGuestVacuum()
unsolv_old_system, old_positions, top_old = host_guest.system, host_guest.positions, host_guest.topology
ligand_topology = [res for res in top_old.residues()]
current_mol = forcefield_generators.generateOEMolFromTopologyResidue(
ligand_topology[1]) # guest is second residue in topology
proposed_mol = smiles_to_oemol('C1CC2(CCC1(CC2)C)C')
initial_smiles = oechem.OEMolToSmiles(current_mol)
final_smiles = oechem.OEMolToSmiles(proposed_mol)
gaff_xml_filename = get_data_filename("data/gaff.xml")
forcefield = app.ForceField(gaff_xml_filename, 'tip3p.xml')
forcefield.registerTemplateGenerator(
forcefield_generators.gaffTemplateGenerator)
solvated_system = forcefield.createSystem(top_old, removeCMMotion=False)
gaff_filename = get_data_filename('data/gaff.xml')
system_generator = SystemGenerator(
[gaff_filename, 'amber99sbildn.xml', 'tip3p.xml'],
forcefield_kwargs={
'removeCMMotion': False,
'nonbondedMethod': app.NoCutoff
})
geometry_engine = geometry.FFAllAngleGeometryEngine()
proposal_engine = SmallMoleculeSetProposalEngine(
[initial_smiles, final_smiles],
system_generator,
residue_name=current_mol_name)
#generate topology proposal
topology_proposal = proposal_engine.propose(solvated_system,
top_old,
current_mol=current_mol,
proposed_mol=proposed_mol)
#generate new positions with geometry engine
new_positions, _ = geometry_engine.propose(topology_proposal,
old_positions, beta)
return topology_proposal, old_positions, new_positions
def generate_solvated_hybrid_test_topology(current_mol_name="naphthalene",
proposed_mol_name="benzene",
current_mol_smiles=None,
proposed_mol_smiles=None,
vacuum=False,
render_atom_mapping=False):
"""
This function will generate a topology proposal, old positions, and new positions with a geometry proposal (either vacuum or solvated) given a set of input iupacs or smiles.
The function will (by default) read the iupac names first. If they are set to None, then it will attempt to read a set of current and new smiles.
An atom mapping pdf will be generated if specified.
Arguments
----------
current_mol_name : str, optional
name of the first molecule
proposed_mol_name : str, optional
name of the second molecule
current_mol_smiles : str (default None)
current mol smiles
proposed_mol_smiles : str (default None)
proposed mol smiles
vacuum: bool (default False)
whether to render a vacuum or solvated topology_proposal
render_atom_mapping : bool (default False)
whether to render the atom map of the current_mol_name and proposed_mol_name
Returns
-------
topology_proposal : perses.rjmc.topology_proposal
The topology proposal representing the transformation
current_positions : np.array, unit-bearing
The positions of the initial system
new_positions : np.array, unit-bearing
The positions of the new system
"""
import simtk.openmm.app as app
from openmoltools import forcefield_generators
from openeye import oechem
from openmoltools.openeye import iupac_to_oemol, generate_conformers, smiles_to_oemol
from openmoltools import forcefield_generators
import perses.utils.openeye as openeye
from perses.utils.data import get_data_filename
from perses.rjmc.topology_proposal import TopologyProposal, SystemGenerator, SmallMoleculeSetProposalEngine
import simtk.unit as unit
from perses.rjmc.geometry import FFAllAngleGeometryEngine
if current_mol_name != None and proposed_mol_name != None:
try:
old_oemol, new_oemol = iupac_to_oemol(
current_mol_name), iupac_to_oemol(proposed_mol_name)
old_smiles = oechem.OECreateSmiString(
old_oemol,
oechem.OESMILESFlag_DEFAULT | oechem.OESMILESFlag_Hydrogens)
new_smiles = oechem.OECreateSmiString(
new_oemol,
oechem.OESMILESFlag_DEFAULT | oechem.OESMILESFlag_Hydrogens)
except:
raise Exception(
f"either {current_mol_name} or {proposed_mol_name} is not compatible with 'iupac_to_oemol' function!"
)
elif current_mol_smiles != None and proposed_mol_smiles != None:
try:
old_oemol, new_oemol = smiles_to_oemol(
current_mol_smiles), smiles_to_oemol(proposed_mol_smiles)
old_smiles = oechem.OECreateSmiString(
old_oemol,
oechem.OESMILESFlag_DEFAULT | oechem.OESMILESFlag_Hydrogens)
new_smiles = oechem.OECreateSmiString(
new_oemol,
oechem.OESMILESFlag_DEFAULT | oechem.OESMILESFlag_Hydrogens)
except:
raise Exception(f"the variables are not compatible")
else:
raise Exception(
f"either current_mol_name and proposed_mol_name must be specified as iupacs OR current_mol_smiles and proposed_mol_smiles must be specified as smiles strings."
)
old_oemol, old_system, old_positions, old_topology = openeye.createSystemFromSMILES(
old_smiles, title="MOL")
#correct the old positions
old_positions = openeye.extractPositionsFromOEMol(old_oemol)
old_positions = old_positions.in_units_of(unit.nanometers)
new_oemol, new_system, new_positions, new_topology = openeye.createSystemFromSMILES(
new_smiles, title="NEW")
ffxml = forcefield_generators.generateForceFieldFromMolecules(
[old_oemol, new_oemol])
old_oemol.SetTitle('MOL')
new_oemol.SetTitle('MOL')
old_topology = forcefield_generators.generateTopologyFromOEMol(old_oemol)
new_topology = forcefield_generators.generateTopologyFromOEMol(new_oemol)
if not vacuum:
nonbonded_method = app.PME
barostat = openmm.MonteCarloBarostat(1.0 * unit.atmosphere,
300.0 * unit.kelvin, 50)
else:
nonbonded_method = app.NoCutoff
barostat = None
gaff_xml_filename = get_data_filename("data/gaff.xml")
system_generator = SystemGenerator(
[gaff_xml_filename, 'amber99sbildn.xml', 'tip3p.xml'],
barostat=barostat,
forcefield_kwargs={
'removeCMMotion': False,
'nonbondedMethod': nonbonded_method,
'constraints': app.HBonds,
'hydrogenMass': 4.0 * unit.amu
})
system_generator._forcefield.loadFile(StringIO(ffxml))
proposal_engine = SmallMoleculeSetProposalEngine([old_smiles, new_smiles],
system_generator,
residue_name='MOL')
geometry_engine = FFAllAngleGeometryEngine(metadata=None,
use_sterics=False,
n_bond_divisions=1000,
n_angle_divisions=180,
n_torsion_divisions=360,
verbose=True,
storage=None,
bond_softening_constant=1.0,
angle_softening_constant=1.0,
neglect_angles=False)
if not vacuum:
#now to solvate
modeller = app.Modeller(old_topology, old_positions)
hs = [
atom for atom in modeller.topology.atoms()
if atom.element.symbol in ['H']
and atom.residue.name not in ['MOL', 'OLD', 'NEW']
]
modeller.delete(hs)
modeller.addHydrogens(forcefield=system_generator._forcefield)
modeller.addSolvent(system_generator._forcefield,
model='tip3p',
padding=9.0 * unit.angstroms)
solvated_topology = modeller.getTopology()
solvated_positions = modeller.getPositions()
solvated_positions = unit.quantity.Quantity(value=np.array([
list(atom_pos) for atom_pos in
solvated_positions.value_in_unit_system(unit.md_unit_system)
]),
unit=unit.nanometers)
solvated_system = system_generator.build_system(solvated_topology)
#now to create proposal
top_proposal = proposal_engine.propose(
current_system=solvated_system,
current_topology=solvated_topology,
current_mol=old_oemol,
proposed_mol=new_oemol)
new_positions, _ = geometry_engine.propose(top_proposal,
solvated_positions, beta)
if render_atom_mapping:
from perses.utils.smallmolecules import render_atom_mapping
print(
f"new_to_old: {proposal_engine.non_offset_new_to_old_atom_map}"
)
render_atom_mapping(f"{old_smiles}to{new_smiles}.png", old_oemol,
new_oemol,
proposal_engine.non_offset_new_to_old_atom_map)
return top_proposal, solvated_positions, new_positions
else:
vacuum_system = system_generator.build_system(old_topology)
top_proposal = proposal_engine.propose(current_system=vacuum_system,
current_topology=old_topology,
current_mol=old_oemol,
proposed_mol=new_oemol)
new_positions, _ = geometry_engine.propose(top_proposal, old_positions,
beta)
if render_atom_mapping:
from perses.utils.smallmolecules import render_atom_mapping
print(f"new_to_old: {top_proposal._new_to_old_atom_map}")
render_atom_mapping(f"{old_smiles}to{new_smiles}.png", old_oemol,
new_oemol, top_proposal._new_to_old_atom_map)
return top_proposal, old_positions, new_positions
""" Test fragmentation """
__author__ = 'Chaya D. Stern'
from torsionfit.tests.utils import get_fun, has_openeye
import unittest
if has_openeye:
from openmoltools.openeye import get_charges, smiles_to_oemol
import openeye.oechem as oechem
from torsionfit.qmscan import fragment
mol = smiles_to_oemol('CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4')
charged = get_charges(mol, keep_confs=1)
class TestFragments(unittest.TestCase):
@unittest.skipUnless(has_openeye, "Cannot test without OpenEye")
def test_tag_funcgroup(self):
""" Test tag functional groups """
tagged_funcgroups = fragment._tag_fgroups(charged)
self.assertEquals(len(tagged_funcgroups), 3)
atom_idx = tagged_funcgroups['amide_0'][0].pop()
atom = charged.GetAtom(oechem.OEHasAtomIdx(atom_idx))
fgroup = atom.GetData('fgroup')
self.assertEquals('amide_0', fgroup)
@unittest.skipUnless(has_openeye, "Cannot test without OpenEye")
def test_tag_rings(self):
""" Test tag rings"""
tagged_rings = fragment._tag_rings(charged)
self.assertEquals(len(tagged_rings), 3)
