def MakeAlpha(ifs, ofs):
phival = math.pi / -3.0
psival = math.pi / -3.0
chival = math.pi
nrphis = 0
nrpsis = 0
nrchis = 0
mol = oechem.OEGraphMol()
while oechem.OEReadMolecule(ifs, mol):
if not oechem.OEHasResidues(mol):
oechem.OEPerceiveResidues(mol, oechem.OEPreserveResInfo_All)
# remove cross-links
for bond in mol.GetBonds():
if bond.GetBgn().GetAtomicNum() == oechem.OEElemNo_S and \
bond.GetEnd().GetAtomicNum() == oechem.OEElemNo_S:
mol.DeleteBond(bond)
oechem.OEFindRingAtomsAndBonds(mol)
hv = oechem.OEHierView(mol)
for res in hv.GetResidues():
if not oechem.OEIsStandardProteinResidue(res):
continue
# set psi and phi angles
if not oechem.OESetTorsion(res, oechem.OEProtTorType_Phi, phival):
oeres = res.GetOEResidue()
print("Unable to set phi for %s %d" %
(oeres.GetName(), oeres.GetResidueNumber()))
else:
nrphis += 1
if not oechem.OESetTorsion(res, oechem.OEProtTorType_Psi, psival):
oeres = res.GetOEResidue()
print("Unable to set psi for %s %d" %
(oeres.GetName(), oeres.GetResidueNumber()))
else:
nrpsis += 1
# set chis
if oechem.OEGetResidueIndex(
res.GetOEResidue().GetName()) == oechem.OEResidueIndex_PRO:
continue # It does not make sense to set Proline chi angles to 180
for chi in oechem.OEGetChis(res):
if not oechem.OESetTorsion(res, chi, chival):
oeres = res.GetOEResidue()
print("Unable to set chi %s for %s %d" %
(oechem.OEGetProteinTorsionName(chi),
oeres.GetName(), oeres.GetResidueNumber()))
else:
nrchis += 1
oechem.OEWriteMolecule(ofs, mol)
print(nrphis, " phi torsion angle set to ", phival * oechem.cvar.Rad2Deg)
print(nrpsis, " psi torsion angle set to ", psival * oechem.cvar.Rad2Deg)
print(nrchis, " chis torsion angle set to ", chival * oechem.cvar.Rad2Deg)
def gen_torsional_confs(mol, dih, num_points, include_input=False):
"""Drives the primary torsion in the molecule and generates labeled
torsional conformers.
Inputs:
mol - OEMol
must have a 'CONFORMER_LABEL' in the sd_data
"""
angle_list = [2*i*oechem.Pi/num_points for i in range(num_points)]
dih_atoms = [x for x in dih.GetAtoms()]
# Create new output OEMol
torsion_conformers = oechem.OEMol(mol)
if not include_input:
torsion_conformers.DeleteConfs()
for conf_id, conf in enumerate(mol.GetConfs()):
conf_name = get_sd_data(conf, 'CONFORMER_LABEL')
for angle_idx, angle in enumerate(angle_list):
angle_deg = int(round(angle*oechem.Rad2Deg))
oechem.OESetTorsion(conf,
dih_atoms[0], dih_atoms[1], dih_atoms[2], dih_atoms[3],
angle)
new_conf = torsion_conformers.NewConf(conf)
new_conf.SetDimension(3)
new_conf_name = conf_name + '_{:02d}'.format(angle_idx)
oechem.OESetSDData(new_conf, 'CONFORMER_LABEL', new_conf_name)
oechem.OESetSDData(new_conf, 'TORSION_ANGLE', "{:.0f}".format(angle_deg))
new_conf.SetDoubleData('TORSION_ANGLE', angle_deg)
new_conf.SetTitle('{}: Angle {:.0f}'.format(conf_name, angle_deg))
return torsion_conformers
def generate_grid_conformers(molecule,
dihedrals,
intervals,
max_rotation=360,
copy_mol=True):
"""
Generate conformers using torsion angle grids.
Parameters
----------
molecule: OEMol
dihedrals: list of
intervals
Returns
-------
"""
# molecule must be mapped
if copy_mol:
molecule = copy.deepcopy(molecule)
if cmiles.utils.has_atom_map(molecule):
remove_map(molecule)
else:
raise ValueError("Molecule must have map indices")
# Check length of dihedrals match length of intervals
conf_mol = generate_conformers(molecule, max_confs=1)
conf = conf_mol.GetConfs().next()
coords = oechem.OEFloatArray(conf.GetMaxAtomIdx() * 3)
conf.GetCoords(coords)
torsions = [[conf_mol.GetAtom(oechem.OEHasMapIdx(i + 1)) for i in dih]
for dih in dihedrals]
for i, tor in enumerate(torsions):
copy_conf_mol = copy.deepcopy(conf_mol)
conf_mol.DeleteConfs()
for conf in copy_conf_mol.GetConfs():
coords = oechem.OEFloatArray(conf.GetMaxAtomIdx() * 3)
conf.GetCoords(coords)
for angle in range(5, max_rotation + 5, intervals[i]):
newconf = conf_mol.NewConf(coords)
oechem.OESetTorsion(newconf, tor[0], tor[1], tor[2], tor[3],
radians(angle))
restore_map(conf_mol)
return conf_mol
def get_best_conf(mol, dih, num_points):
"""Drive the primary torsion in the molecule and select the lowest
energy conformer to represent each dihedral angle
"""
delta = 360.0 / num_points
angle_list = [2 * i * oechem.Pi / num_points for i in range(num_points)]
dih_atoms = [x for x in dih.GetAtoms()]
# Create new output OEMol
title = mol.GetTitle()
tor_mol = oechem.OEMol()
opts = oeszybki.OETorsionScanOptions()
opts.SetDelta(delta)
opts.SetForceFieldType(oeszybki.OEForceFieldType_MMFF94)
opts.SetSolvationType(oeszybki.OESolventModel_NoSolv)
tmp_angle = 0.0
tor = oechem.OETorsion(dih_atoms[0], dih_atoms[1], dih_atoms[2],
dih_atoms[3], tmp_angle)
oeszybki.OETorsionScan(tor_mol, mol, tor, opts)
oechem.OECopySDData(tor_mol, mol)
# if 0 and 360 sampled because of rounding
if tor_mol.NumConfs() > num_points:
for conf in tor_mol.GetConfs():
continue
tor_mol.DeleteConf(conf)
for angle, conf in zip(angle_list, tor_mol.GetConfs()):
angle_deg = int(round(angle * oechem.Rad2Deg))
tor_mol.SetActive(conf)
oechem.OESetTorsion(conf, dih_atoms[0], dih_atoms[1], dih_atoms[2],
dih_atoms[3], angle)
conf_name = title + '_{:02d}'.format(conf.GetIdx())
oechem.OESetSDData(conf, 'CONFORMER_LABEL', conf_name)
oechem.OESetSDData(conf, 'TORSION_ANGLE', "{:.0f}".format(angle_deg))
conf.SetDoubleData('TORSION_ANGLE', angle_deg)
conf.SetTitle('{}: Angle {:.0f}'.format(conf_name, angle_deg))
return tor_mol
def generate_constraint_opt_input(qc_molecule, dihedrals, maximum_rotation=30, interval=5, filename=None):
"""
Parameters
----------
qc_molecule
dihedrals
Returns
-------
QCFractal optimization jobs input
"""
from openeye import oechem
optimization_jobs = {}
tagged_smiles = qc_molecule['identifiers']['canonical_isomeric_explicit_hydrogen_mapped_smiles']
mol = oechem.OEMol()
oechem.OESmilesToMol(mol, tagged_smiles)
atom_map = get_atom_map(mol, tagged_smiles)
coords = chemi.from_mapped_xyz_to_mol_idx_order(qc_molecule['geometry'], atom_map)
# convert coord to Angstrom
coords = coords * utils.BOHR_2_ANGSTROM
conf = mol.GetConfs().next()
conf.SetCoords(oechem.OEFloatArray(coords))
# new molecule for setting dihedral angles
mol_2 = oechem.OEMol(mol)
conf_2 = mol_2.GetConfs().next()
coords_2 = oechem.OEFloatArray(conf_2.GetMaxAtomIdx()*3)
conf.GetCoords(coords_2)
mol_2.DeleteConfs()
interval = radians(interval)
max_rot = radians(maximum_rotation)
for dihedral in dihedrals:
#j = 0
dih_idx = dihedrals[dihedral]
tor = []
for i in dih_idx:
a = mol.GetAtom(oechem.OEHasMapIdx(i+1))
tor.append(a)
dih_angle = oechem.OEGetTorsion(conf, tor[0], tor[1], tor[2], tor[3])
for i, angle in enumerate(np.arange(dih_angle-max_rot, dih_angle+max_rot, interval)):
newconf = mol.NewConf(coords_2)
oechem.OESetTorsion(newconf, tor[0], tor[1], tor[2], tor[3], angle)
#new_angle = oechem.OEGetTorsion(newconf, tor[0], tor[1], tor[2], tor[3])
# if new_angle == dih_angle:
# j += 1
# if j > 1:
# # One equivalent angle should be generated.
# logger().warning("Openeye did not generate a new conformer for torsion and angle {} {}. Will not generate"
# "qcfractal optimizaiton input".format(dih_idx, angle))
# break
if filename:
pdb = oechem.oemolostream("{}_{}.pdb".format(filename, i))
oechem.OEWritePDBFile(pdb, newconf)
symbols, geometry = chemi.to_mapped_geometry(newconf, atom_map)
qc_molecule = copy.deepcopy(qc_molecule)
qc_molecule['geometry'] = geometry
qc_molecule['symbols'] = symbols
degree = degrees(angle)
optimization_jobs['{}_{}'.format(dih_idx, int(round(degree)))] = {
'type': 'optimization_input',
'initial_molecule': qc_molecule,
'dihedral': dih_idx,
'constraints': {
"set": [{
"type": "dihedral",
"indices": dih_idx,
"value": degree
}]
}
}
return optimization_jobs
def process(self, mol, port):
"""
The input to this cube will be an OEMol with one or more conformers
with "CONFORMER_LABEL" SD Data of the form 'XY-1234567_1_2_3_4_00_00'
"""
num_confs = mol.NumConfs()
last_conf = mol.GetActive()
last_conf_name = oechem.OEGetSDData(last_conf, "CONFORMER_LABEL")
self.log.info(
"Processing conformer {} on {} at {:%Y-%m-%d %H:%M:%S}".format(
last_conf_name, os.environ["HOSTNAME"],
datetime.datetime.now()))
if num_confs == self.args.num_points:
self.success.emit(mol)
self.log.info(
"Completed scan for {} on {} at {:%Y-%m-%d %H:%M:%S}".format(
mol.GetTitle(), os.environ["HOSTNAME"],
datetime.datetime.now()))
return
if num_confs == 1 and not mol.HasData(self.conf_selection_tag):
self.log.info(
"Conformer {} is a fresh starting conformer on {} at {:%Y-%m-%d %H:%M:%S}"
.format(mol.GetTitle(), os.environ["HOSTNAME"],
datetime.datetime.now()))
mol.SetIntData(self.conf_selection_tag, last_conf.GetIdx())
last_conf.SetDoubleData("TORSION_ANGLE", 0.0)
oechem.OESetSDData(last_conf, "TORSION_ANGLE", "0.0")
self.log.info(
"Sending conformer {} to energy calculation from {} at {:%Y-%m-%d %H:%M:%S}"
.format(last_conf_name, os.environ["HOSTNAME"],
datetime.datetime.now()))
self.to_energy_calc.emit(mol)
return
try:
torsion_tag = "TORSION_ATOMS_FRAGMENT"
torsion_atoms_in_fragment = get_sd_data(mol, torsion_tag).split()
dihedral_atom_indices = [
int(x) - 1 for x in torsion_atoms_in_fragment
]
dih, _ = get_dihedral(mol, dihedral_atom_indices)
dih_atoms = [x for x in dih.GetAtoms()]
# if the last energy calculation failed
if not oechem.OEHasSDData(last_conf, "PSI4_ENERGY"):
self.log.info(
"Conformer {} found to have NO ENERGY on {} at {:%Y-%m-%d %H:%M:%S}"
.format(last_conf_name, os.environ["HOSTNAME"],
datetime.datetime.now()))
mol.PopActive()
last_conf = mol.GetActive()
new_conf = mol.NewConf(last_conf)
mol.PushActive(new_conf)
conf_no = num_confs
conformer_label = last_conf_name[:-3] + "_{:02d}".format(conf_no)
oechem.OESetSDData(new_conf, "CONFORMER_LABEL", conformer_label)
angle = num_confs * 2 * oechem.Pi / self.args.num_points
angle_deg = oechem.Rad2Deg * angle
new_conf.SetDoubleData("TORSION_ANGLE", angle_deg)
oechem.OESetSDData(new_conf, "TORSION_ANGLE",
"{:.1f}".format(angle_deg))
if not oechem.OESetTorsion(new_conf, dih_atoms[0], dih_atoms[1],
dih_atoms[2], dih_atoms[3], angle):
self.log.error(
"Could not rotate conformer {} by {:.1f} on {} at {:%Y-%m-%d %H:%M:%S}"
.format(
last_conf_name,
angle_deg,
os.environ["HOSTNAME"],
datetime.datetime.now(),
))
mol.SetIntData(self.conf_selection_tag, new_conf.GetIdx())
self.log.info(
"Sending conformer {} to energy calculation from {} at {:%Y-%m-%d %H:%M:%S}"
.format(conformer_label, os.environ["HOSTNAME"],
datetime.datetime.now()))
self.to_energy_calc.emit(mol)
except Exception as e:
self.log.error(
"COuld not drive torsion in conformer {} on {} at {:%Y-%m-%d %H:%M:%S}: {}"
.format(last_conf_name, os.environ["HOSTNAME"],
datetime.datetime.now(), e))
self.failure.emit(mol)
def generate_torsions(inp_mol,
output_path,
interval,
base_name=None,
tar=True):
"""
This function takes a 3D molecule (pdf, mol2 or sd file) and generates structures for a torsion drive on all torsions
in the molecule. This function uses OpenEye
Parameters
----------
mol : OEMol
molecule to generate 1D torsion scans
output_path: str
path to output file directory
interval: int
angle (in degrees) of interval for torsion drive
base_name: str
base name for file. Default is None. If default, use title in OEMol for base name
tar: bool
If true, will compress output
"""
if not base_name:
base_name = inp_mol.GetTitle()
mid_tors = [[tor.a, tor.b, tor.c, tor.d]
for tor in oechem.OEGetTorsions(inp_mol)]
# This smarts should match terminal torsions such as -CH3, -NH2, -NH3+, -OH, and -SH
smarts = '[*]~[*]-[X2H1,X3H2,X4H3]-[#1]'
qmol = oechem.OEQMol()
if not oechem.OEParseSmarts(qmol, smarts):
warnings.warn('OEParseSmarts failed')
ss = oechem.OESubSearch(qmol)
mol = oechem.OEMol(inp_mol)
h_tors = []
oechem.OEPrepareSearch(mol, ss)
unique = True
for match in ss.Match(mol, unique):
tor = []
for ma in match.GetAtoms():
tor.append(ma.target)
h_tors.append(tor)
# Combine middle and terminal torsions
all_tors = mid_tors + h_tors
# Sort all_tors so that it's grouped by central bond
central_bonds = np.zeros((len(all_tors), 3), dtype=int)
for i, tor in enumerate(all_tors):
central_bonds[i][0] = i
central_bonds[i][1] = tor[1].GetIdx()
central_bonds[i][2] = tor[2].GetIdx()
grouped = central_bonds[central_bonds[:, 2].argsort()]
sorted_tors = [all_tors[i] for i in grouped[:, 0]]
# Keep only one torsion per rotatable bond
tors = []
best_tor = [
sorted_tors[0][0], sorted_tors[0][0], sorted_tors[0][0],
sorted_tors[0][0]
]
first_pass = True
for tor in sorted_tors:
logger().info("Idxs: {} {} {} {}".format(tor[0].GetIdx(),
tor[1].GetIdx(),
tor[2].GetIdx(),
tor[3].GetIdx()))
logger().info("Atom Numbers: {} {} {} {}".format(
tor[0].GetAtomicNum(), tor[1].GetAtomicNum(),
tor[2].GetAtomicNum(), tor[3].GetAtomicNum()))
if tor[1].GetIdx() != best_tor[1].GetIdx() or tor[2].GetIdx(
) != best_tor[2].GetIdx():
new_tor = True
if not first_pass:
logger().info("Adding to list: {} {} {} {}".format(
best_tor[0].GetIdx(), best_tor[1].GetIdx(),
best_tor[2].GetIdx(), best_tor[3].GetIdx()))
tors.append(best_tor)
first_pass = False
best_tor = tor
best_tor_order = tor[0].GetAtomicNum() + tor[3].GetAtomicNum()
logger().info(
"new_tor with central bond across atoms: {} {}".format(
tor[1].GetIdx(), tor[2].GetIdx()))
else:
logger().info("Not a new_tor but now with end atoms: {} {}".format(
tor[0].GetIdx(), tor[3].GetIdx()))
tor_order = tor[0].GetAtomicNum() + tor[3].GetAtomicNum()
if tor_order > best_tor_order:
best_tor = tor
best_tor_order = tor_order
logger().info("Adding to list: {} {} {} {}".format(best_tor[0].GetIdx(),
best_tor[1].GetIdx(),
best_tor[2].GetIdx(),
best_tor[3].GetIdx()))
tors.append(best_tor)
logger().info("List of torsion to drive:")
for tor in tors:
logger().info("Idx: {} {} {} {}".format(tor[0].GetIdx(),
tor[1].GetIdx(),
tor[2].GetIdx(),
tor[3].GetIdx()))
logger().info("Atom numbers: {} {} {} {}".format(
tor[0].GetAtomicNum(), tor[1].GetAtomicNum(),
tor[2].GetAtomicNum(), tor[3].GetAtomicNum()))
conf = mol.GetConfs().next()
coords = oechem.OEFloatArray(conf.GetMaxAtomIdx() * 3)
conf.GetCoords(coords)
# Check if coordinates are not zero
values = np.asarray(
[coords.__getitem__(i) == 0 for i in range(coords.__len__())])
if values.all():
# Generate new coordinates.
mol2 = generate_conformers(mol, max_confs=1)
conf = mol2.GetConfs().next()
coords = oechem.OEFloatArray(conf.GetMaxAtomIdx() * 3)
conf.GetCoords(coords)
mol2.DeleteConfs()
mol.DeleteConfs()
for tor in tors:
tor_name = str((tor[0].GetIdx()) + 1) + '_' + str(
(tor[1].GetIdx()) + 1) + '_' + str(
(tor[2].GetIdx()) + 1) + '_' + str((tor[3].GetIdx()) + 1)
folder = os.path.join(output_path, tor_name)
try:
os.makedirs(folder)
except FileExistsError:
logger().info("Overwriting existing directory {}".format(tor_name))
for angle in range(0, 360, interval):
angle_folder = os.path.join(folder, str(angle))
try:
os.mkdir(angle_folder)
except FileExistsError:
logger().info(
"Overwriting existing directory {}".format(tor_name))
newconf = mol.NewConf(coords)
oechem.OESetTorsion(newconf, tor[0], tor[1], tor[2], tor[3],
radians(angle))
pdb = oechem.oemolostream('{}/{}_{}_{}.pdb'.format(
angle_folder, base_name, tor_name, angle))
oechem.OEWritePDBFile(pdb, newconf)
if tar:
# tar archive output
out = tarfile.open('{}.tar.gz'.format(output_path), mode='w:gz')
os.chdir(output_path)
os.chdir('../')
out.add('{}'.format(base_name))
out.close()