def CisCheck(ifs):
nrmol = 0
nrcis = 0
mol = oechem.OEGraphMol()
while oechem.OEReadMolecule(ifs, mol):
nrmol += 1
print("===========================================================")
print("Molecule: %s Title: %s" % (nrmol, mol.GetTitle()))
if not oechem.OEHasResidues(mol):
oechem.OEPerceiveResidues(mol, oechem.OEPreserveResInfo_All)
hv = oechem.OEHierView(mol)
resiter = oechem.ConstOEHierResidueIter()
resiter = hv.GetResidues()
while (resiter.IsValid()):
res = resiter.Target()
resiter.Next()
if not oechem.OEIsStandardProteinResidue(res):
continue
torsion = oechem.OEGetTorsion(res, oechem.OEProtTorType_Omega)
if torsion != -100.0:
if torsion < math.pi / 2.0 and torsion > -math.pi / 2.0:
if resiter.IsValid():
nextres = resiter.Target()
oenextres = nextres.GetOEResidue()
if oechem.OEGetResidueIndex(
oenextres) == oechem.OEResidueIndex_PRO:
continue
nrcis += 1
oeres = res.GetOEResidue()
print("%s %s %2d omega torsion = %.2f degree" %
(oeres.GetName(), oeres.GetChainID(),
oeres.GetResidueNumber(),
torsion * oechem.cvar.Rad2Deg))
print(" %d cis amide bond(s) identified\n" % nrcis)
def set_weighted_dihedral_histograms(mol, itag, work, nrbins):
"""
Iterates over the dihedral groups and bins the torsional
angles for each conformation. The histogram data is then
attached to the groups with the given tag.
:type mol: oechem.OEMol
:type itag: int
:type nrbins: int
"""
angleinc = 360.0 / float(nrbins)
# scale and normalize
work = list(normalize(np.array(work) - min(work)))
for group in mol.GetGroups(oechem.OEHasGroupType(itag)):
atoms = oechem.OEAtomVector()
for atom in group.GetAtoms():
atoms.append(atom)
histogram = [0] * nrbins
for idx, conf in enumerate(mol.GetConfs()):
rad = oechem.OEGetTorsion(conf, atoms[0], atoms[1], atoms[2],
atoms[3])
deg = math.degrees(rad)
deg = (deg + 360.0) % 360.0
binidx = int(math.floor((deg / angleinc)))
# instaed of 1 add the weight
histogram[binidx] += np.exp(work[idx])
group.SetData(itag, histogram)
def extract_molecule_torsion_data(parent_mol, frag_mols=None):
"""
extract dihedral angle associated with each torsion motif in the input molecule
Torsion motifs are represented using generic modified inchi (central two atoms)
and specific modified inchi (4 torsion atoms)
@param parent_mol:
@type parent_mol: oechem.OEGraphMol
@return: tuple(str, dict[str, list[float]])
"""
if frag_mols is None:
frag_mols = get_molecule_torsion_fragments(parent_mol)
torsion_data = collections.defaultdict(list)
for frag_mol in frag_mols:
inchi_key = oechem.OECreateInChIKey(frag_mol)
atom_map = get_fragment_to_parent_atom_mapping(parent_mol, frag_mol)
try:
_, b, c, _ = get_torsion_oeatom_list(frag_mol)
for a in b.GetAtoms(oechem.OEIsHeavy()):
for d in c.GetAtoms(oechem.OEIsHeavy()):
if a.GetIdx() == c.GetIdx() or d.GetIdx() == b.GetIdx():
continue
ap = atom_map[a]
bp = atom_map[b]
cp = atom_map[c]
dp = atom_map[d]
if (a.GetAtomicNum() == ap.GetAtomicNum()
and b.GetAtomicNum() == bp.GetAtomicNum()
and c.GetAtomicNum() == cp.GetAtomicNum()
and d.GetAtomicNum() == dp.GetAtomicNum()):
angle = (
oechem.OEGetTorsion(parent_mol, ap, bp, cp, dp) *
oechem.Rad2Deg)
torsion_inchi = inchi_key + get_modified_inchi_key(
frag_mol, [a, b, c, d])
torsion_data[torsion_inchi].append(
(ap.GetIdx(), bp.GetIdx(), cp.GetIdx(),
dp.GetIdx(), angle))
except Exception as e:
logging.warning(e)
continue
parent_inchi = get_modified_molecule_inchi(parent_mol)
return (parent_inchi, torsion_data)
def set_dihedral(mol, itag):
"""
Iterates over the dihedral groups and attaches the
dihedral angle to the group with the given tag.
:type mol: oechem.OEMol
:type itag: int
"""
for group in mol.GetGroups(oechem.OEHasGroupType(itag)):
atoms = oechem.OEAtomVector()
for atom in group.GetAtoms():
atoms.append(atom)
rad = oechem.OEGetTorsion(mol, atoms[0], atoms[1], atoms[2], atoms[3])
deg = math.degrees(rad)
deg = (deg + 360.0) % 360.0
group.SetData(itag, deg)
def get_closest_dihedral_angle(mol, dihedral, ref_dihedral, itag):
"""
Returns the closest torsion angle difference to the reference.
:type mol: oechem.OEMol
:type dihedral: oechem.OEGroupBase
:type ref_dihedral: oechem.OEGroupBase
:type itag: int
"""
closest_angle = float("inf")
for conf in mol.GetConfs():
atoms = [a for a in dihedral.GetAtoms()]
rad = oechem.OEGetTorsion(conf, atoms[0], atoms[1], atoms[2], atoms[3])
deg = math.degrees(rad)
angle_diff = (abs(deg - ref_dihedral.GetData(itag)) + 360) % 360
closest_angle = min(closest_angle, angle_diff)
return closest_angle
def generate_torsional_strain(mol):
'''
Calculate strain energy of each rotatable bond using attached ML profiles
@param mol: OEGraphMol
@param gen_confs: bool
@param num_confs: int
@return: None
'''
for bond in mol.GetBonds(oechem.OEIsRotor()):
if bond.HasData(ENERGY_PROFILE_TAG):
energy_profile = bond.GetData(ENERGY_PROFILE_TAG)
x, y = extract_numeric_data_from_profile_str(energy_profile)
_, f = get_global_min_interp1d(x, y)
bond_strain = 1e10
torsion_atoms_list = extract_torsion_atoms(mol, bond)
for torsion_atoms in torsion_atoms_list:
a, b, c, d = torsion_atoms
angle = oechem.OEGetTorsion(mol, a, b, c, d) * oechem.Rad2Deg
strainE = float(f(angle))
if strainE < 0.0:
strainE = 0.0
if bond_strain > strainE:
bond_strain = strainE
tor_atoms_str = ' '.join(
list(
map(str,
[a.GetIdx(),
b.GetIdx(),
c.GetIdx(),
d.GetIdx()])))
bond.SetData(TORSION_ATOMS_FRAGMENT_TAG, tor_atoms_str)
bond.SetData(STRAIN_TAG, bond_strain)
if mol.HasData(HAS_PROFILES_TAG) and mol.GetData(HAS_PROFILES_TAG):
save_profile_as_sd(mol)
return mol
def GetThetaIJKLMatrix(mol, iAtoms, jAtom, kAtom, lAtoms, transform=True):
'''
Using the given input, calculates a matrix of torsion angles around jk
jAtom, kAtom -> OEAtombase, middle two atoms of the torsion
iAtoms -> list of N OEAtombase
lAtoms -> list of M OEAtombase
return a N-by-M matrix of angle theta_ijkl
'''
torsions = []
for iAtom in iAtoms:
for lAtom in lAtoms:
tor_angle = oechem.OEGetTorsion(mol, iAtom, jAtom, kAtom, lAtom)
if not transform:
torsions.append(tor_angle)
else:
torsions.append((math.pi + tor_angle) / 4.0)
theta_ijkl = np.array(torsions)
theta_ijkl = theta_ijkl.reshape(len(iAtoms), len(lAtoms))
return theta_ijkl
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 CalculateTorsionSymmetryFunction(self, envMol, num_iter):
'''
Takes refAtom coordinates from refMol as reference and calculates the angular symmetry
function using envMol atoms
Functional form is described in the DFT-NN review article by Behler, page 30, equations 25 and 26
'''
tsf = []
elemList = self.elemList
nullRet = []
bond = get_torsion_oebond(envMol)
if bond is None:
return nullRet
jAtom = bond.GetBgn()
jcoords = OEDoubleArray(3)
if not envMol.GetCoords(bond.GetBgn(), jcoords):
return nullRet
kAtom = bond.GetEnd()
kcoords = OEDoubleArray(3)
if not envMol.GetCoords(bond.GetEnd(), kcoords):
return nullRet
# tsf.append(bond.GetBgn().GetAtomicNum() * bond.GetEnd().GetAtomicNum());
for inum, iElem in enumerate(elemList):
if num_iter == 1:
iAtoms, icoords = self.GetTorsionEnvAtoms(
iElem, bond.GetBgn(), bond.GetEnd(), envMol)
else:
iAtoms, icoords = self.GetTorsionEnvAtoms(
iElem, bond.GetEnd(), bond.GetBgn(), envMol)
if len(icoords) == 0:
for ita in self.itaVec:
for rc in self.rcTorVec:
for num1, elem in enumerate(elemList):
if num1 < inum:
continue
tsf.append(0.0)
continue
ijX, ijY, ijZ, rij, rij2 = GetPairwiseDistanceMatrix(
icoords, [jcoords])
for lnum, lElem in enumerate(elemList):
if lnum < inum:
continue
if num_iter == 1:
lAtoms, lcoords = self.GetTorsionEnvAtoms(
lElem, bond.GetEnd(), bond.GetBgn(), envMol)
else:
lAtoms, lcoords = self.GetTorsionEnvAtoms(
lElem, bond.GetBgn(), bond.GetEnd(), envMol)
if len(lcoords) == 0:
for ita in self.itaVec:
for rc in self.rcTorVec:
tsf.append(0.0)
continue
klX, klY, klZ, rkl, rkl2 = GetPairwiseDistanceMatrix([kcoords],
lcoords)
ilX, ilY, ilZ, ril, ril2 = GetPairwiseDistanceMatrix(
icoords, lcoords)
theta_ijkl = GetThetaIJKLMatrix(envMol, iAtoms, jAtom, kAtom,
lAtoms)
# angular symmetry function
for ita in self.itaVec:
for rc in self.rcTorVec:
rijMat = np.repeat(rij, rkl.size)
rijMat = rijMat.reshape(rij.size, rkl.size)
rklMat = np.repeat(rkl, rij.size)
rklMat = rklMat.reshape(rkl.size, rij.size)
rklMat = np.transpose(rklMat)
fcRij = np.select(
[rijMat <= rc, rijMat > rc],
[0.5 * (np.cos(np.pi * rijMat / rc) + 1.0), 0.0])
fcRkl = np.select(
[rklMat <= rc, rklMat > rc],
[0.5 * (np.cos(np.pi * rklMat / rc) + 1.0), 0.0])
fcRil = np.select(
[ril <= rc, ril > rc],
[0.5 * (np.cos(np.pi * ril / rc) + 1.0), 0.0])
exponent = ita * (np.square(rijMat) +
np.square(rklMat) + np.square(ril))
term1 = np.power(
(1 + self.lambda1 * np.cos(theta_ijkl)), self.chi)
term2 = np.exp(-exponent)
term3 = (fcRij * fcRkl) * fcRil
sumIL = np.sum(term1 * term2 * term3)
coeff = np.power(2, 1 - self.chi) * sumIL
tsf.append(coeff * jAtom.GetAtomicNum() *
kAtom.GetAtomicNum())
a, b, c, d = get_torsion_oeatom_list(envMol)
tsf.append(oechem.OEGetDistance2(envMol, a, d))
tsf.append(oechem.OEGetDistance2(envMol, b, c))
tsf.append(oechem.OEGetTorsion(envMol, a, b, c, d))
tsf.append(a.GetAtomicNum() * d.GetAtomicNum())
tsf.append(b.GetAtomicNum() * c.GetAtomicNum())
return tsf
def save_profile_as_sd(mol: oechem.OEGraphMol):
oechem.OEDeleteSDData(mol, TOTAL_STRAIN_TAG)
oechem.OESetSDData(mol, TOTAL_STRAIN_TAG, '') # place holder
oechem.OEDeleteSDData(mol, NUM_TORSION_PROFILES_TAG)
oechem.OESetSDData(mol, NUM_TORSION_PROFILES_TAG, '')
oechem.OEDeleteSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG)
oechem.OESetSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG, '')
strain_arr = np.zeros(1)
strain_arr_high_conf_preds = np.zeros(1)
num_torsion_profiles = 0
num_low_confidence_torsions = 0
can_torsions = get_canonical_torsions(mol)
for num, can_torsion in enumerate(can_torsions):
bond = mol.GetBond(can_torsion.b, can_torsion.c)
if bond is not None and bond.HasData(ENERGY_PROFILE_TAG):
num_torsion_profiles += 1
bond_strains = bond.GetData(STRAIN_TAG)
profile_offset = bond.GetData(PROFILE_OFFSET_TAG)
if profile_offset < OFFSET_THRESHOLD and (
not bond.HasData(SKIP_TORSION_TAG)):
strain_arr_high_conf_preds += np.array(bond_strains)
strain_arr += np.array(bond_strains)
offset = bond.GetData(PROFILE_OFFSET_TAG)
profile_str = bond.GetData(ENERGY_PROFILE_TAG)
pred_confidence_value = HIGH_PREDICTION_CONFIDENCE_TAG
if offset > OFFSET_THRESHOLD or bond.HasData(SKIP_TORSION_TAG):
profile_str = 'LOW CONFIDENCE - ' + profile_str
pred_confidence_value = LOW_PREDICTION_CONFIDENCE_TAG
num_low_confidence_torsions += 1
#tor_atoms_str = bond.GetData(TORSION_ATOMS_FRAGMENT_TAG)
#tor_atoms_str_list = tor_atoms_str.split(':')
#a_idx, b_idx, c_idx, d_idx = list(map(int, tor_atoms_str_list[0].split()))
tor_atoms_str1 = bond.GetData(TORSION_ATOMS_FRAGMENT_TAG)
ca, cb, cc, cd = list(map(int, tor_atoms_str1.split()))
apStr = "{}:{}:{}:{}".format(ca + 1, cb + 1, cc + 1, cd + 1)
atom_ca = mol.GetAtom(oechem.OEHasAtomIdx(ca))
atom_cb = mol.GetAtom(oechem.OEHasAtomIdx(cb))
atom_cc = mol.GetAtom(oechem.OEHasAtomIdx(cc))
atom_cd = mol.GetAtom(oechem.OEHasAtomIdx(cd))
angle_float = oechem.OEGetTorsion(mol, atom_ca, atom_cb, atom_cc,
atom_cd) * oechem.Rad2Deg
sd_tag1 = 'TORSION_%s_ATOMS' % (num + 1)
sd_tag2 = 'TORSION_%d_TORSIONNET_%s' % (num + 1,
ENERGY_PROFILE_TAG)
sd_tag3 = 'TORSION_%d_TORSIONNET_PRED_CONFIDENCE' % (num + 1)
sd_tag4 = 'TORSION_%d_TORSIONNET_PROFILE_OFFSET' % (num + 1)
oechem.OEDeleteSDData(mol, sd_tag1)
oechem.OEDeleteSDData(mol, sd_tag2)
oechem.OEDeleteSDData(mol, sd_tag3)
oechem.OEDeleteSDData(mol, sd_tag4)
oechem.OESetSDData(mol, sd_tag1, apStr)
oechem.OESetSDData(mol, sd_tag2, profile_str)
sd_tag6 = 'TORSION_%d_%s' % ((num + 1), STRAIN_TAG)
oechem.OEDeleteSDData(mol, sd_tag6)
oechem.OESetSDData(mol, sd_tag6, '%.1f' % bond_strains)
angle = '%.1f' % angle_float
sd_tag5 = 'TORSION_%d_ANGLE' % (num + 1)
oechem.OEDeleteSDData(mol, sd_tag5)
oechem.OESetSDData(mol, sd_tag5, angle)
oechem.OESetSDData(mol, sd_tag3, pred_confidence_value)
oechem.OESetSDData(mol, sd_tag4, '%.2f' % offset)
strain_str = '%.1f' % strain_arr_high_conf_preds[0]
oechem.OESetSDData(mol, TOTAL_STRAIN_TAG, strain_str)
oechem.OESetSDData(mol, NUM_TORSION_PROFILES_TAG,
str(num_torsion_profiles))
oechem.OESetSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG,
str(num_low_confidence_torsions))
reorder_sd_props(mol)
return mol
def cal_molecule_torsion_strain(mol, profiles_map):
"""
@type mol: oechem.OEGraphMol|oechem.OEMol
:param mol:
:param profiles_map:
:return:
"""
if type(mol) is oechem.OEMol:
graph_mol = oechem.OEGraphMol(mol.GetActive())
data = extract_molecule_torsion_data(graph_mol)
else:
data = extract_molecule_torsion_data(mol)
if data is not None:
_, tor_map = data
if type(mol) is oechem.OEGraphMol:
for tor_inchi, tor_data_list in tor_map.items():
if tor_inchi in profiles_map:
for tor_data in tor_data_list:
_, b_idx, c_idx, _, angle = tor_data
bond = mol.GetBond(
mol.GetAtom(oechem.OEHasAtomIdx(b_idx)),
mol.GetAtom(oechem.OEHasAtomIdx(c_idx)),
)
if bond is not None:
strain_energy = profiles_map[tor_inchi](angle)
if strain_energy < 0:
strain_energy = 0
if (bond.HasData(STRAIN_TAG) and
bond.GetData(STRAIN_TAG) > strain_energy):
bond.SetData(STRAIN_TAG, strain_energy)
total_strain = 0.0
for bond in mol.GetBonds():
if bond.HasData(STRAIN_TAG):
total_strain += bond.GetData(STRAIN_TAG)
mol.SetData(STRAIN_TAG, total_strain)
elif type(mol) is oechem.OEMol:
for conf in mol.GetConfs():
bondIdx2energy = {}
bondIdx2profile = {}
bondIdx2toratoms = {}
bondIdx2angles = {}
for tor_inchi, tor_data_list in tor_map.items():
if tor_inchi in profiles_map:
for tor_data in tor_data_list:
a_idx, b_idx, c_idx, d_idx, _ = tor_data
b_atm = conf.GetAtom(oechem.OEHasAtomIdx(b_idx))
c_atm = conf.GetAtom(oechem.OEHasAtomIdx(c_idx))
bond = conf.GetBond(b_atm, c_atm)
if bond is not None:
a_atm = conf.GetAtom(
oechem.OEHasAtomIdx(a_idx))
d_atm = conf.GetAtom(
oechem.OEHasAtomIdx(d_idx))
angle = (oechem.OEGetTorsion(
conf, a_atm, b_atm, c_atm, d_atm) *
oechem.Rad2Deg)
strain_energy = float(
profiles_map[tor_inchi](angle))
if strain_energy < 0:
strain_energy = 0
x = range(-165, 181, 15)
y = []
for a in x:
y.append(float(profiles_map[tor_inchi](a)))
energy_profile = generate_energy_profile_sd_data_1d(
list(zip(x, y)))
bondIdx = bond.GetIdx()
if bondIdx not in bondIdx2energy:
bondIdx2energy[bondIdx] = strain_energy
bondIdx2profile[bondIdx] = energy_profile
bondIdx2toratoms[bondIdx] = [
a_idx + 1,
b_idx + 1,
c_idx + 1,
d_idx + 1,
]
bondIdx2angles[bondIdx] = angle
elif bondIdx2energy[bondIdx] > strain_energy:
bondIdx2energy[bondIdx] = strain_energy
bondIdx2profile[bondIdx] = energy_profile
bondIdx2toratoms[bondIdx] = [
a_idx + 1,
b_idx + 1,
c_idx + 1,
d_idx + 1,
]
bondIdx2angles[bondIdx] = angle
# sd property place holder
oechem.OESetSDData(conf, "QM_STRAIN", "0.0")
oechem.OESetSDData(conf, "NUM_QM_TORSION_PROFILES", "0")
oechem.OESetSDData(conf, "NUM_MISSING_QM_TORSIONS", "-1")
total_strain = 0.0
tor_idx = 1
for tor_count, bond in enumerate(
conf.GetBonds(oechem.OEIsRotor())):
bidx = bond.GetIdx()
if bidx in bondIdx2energy:
total_strain += bondIdx2energy[bidx]
tmp = ":1%".join(list(map(str,
bondIdx2toratoms[bidx])))
tor_atomprop = "cs1:0:1;1%" + tmp
oechem.OESetSDData(
conf,
"QM_TORSION_ATOMS_%d_" % tor_idx + "ATOMPROP",
tor_atomprop,
)
oechem.OESetSDData(
conf,
"QM_TORSION_%d_" % tor_idx + ENERGY_PROFILE_TAG,
bondIdx2profile[bidx],
)
oechem.OESetSDData(
conf,
"TORSION_ANGLE_%d" % tor_idx,
"%.1f" % bondIdx2angles[bidx],
)
oechem.OESetSDData(
conf,
"QM_STRAIN_TORSION_%d" % tor_idx,
"%.1f" % bondIdx2energy[bidx],
)
tor_idx += 1
oechem.OESetSDData(conf, "QM_STRAIN", "%.1f" % total_strain)
oechem.OESetSDData(conf, "NUM_QM_TORSION_PROFILES",
"%d" % (tor_count + 1))
num_missing_torsions = (tor_count + 1) - (tor_idx - 1)
oechem.OESetSDData(conf, "NUM_MISSING_QM_TORSIONS",
"%d" % num_missing_torsions)
conf.SetData(STRAIN_TAG, total_strain)
