def testMMFFAngleConstraints(self):
m = Chem.MolFromMolBlock(self.molB, True, False)
mp = ChemicalForceFields.MMFFGetMoleculeProperties(m)
ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
self.assertTrue(ff)
ff.MMFFAddAngleConstraint(1, 3, 6, False, 90.0, 90.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertTrue(int(angle) == 90)
ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
self.assertTrue(ff)
ff.MMFFAddAngleConstraint(1, 3, 6, True, -10.0, 10.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertTrue(int(angle) == 100)
ff = ChemicalForceFields.MMFFGetMoleculeForceField(m, mp)
self.assertTrue(ff)
ff.MMFFAddAngleConstraint(1, 3, 6, False, -10.0, 10.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertEquals(int(angle), 10) #(int(angle) == 10)
def testUFFAngleConstraints(self):
m = Chem.MolFromMolBlock(self.molB, True, False)
ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
self.assertTrue(ff)
ff.UFFAddAngleConstraint(1, 3, 6, False, 90.0, 90.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertAlmostEqual(angle, 90, delta=0.1)
ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
self.assertTrue(ff)
ff.UFFAddAngleConstraint(1, 3, 6, True, -10.0, 10.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertAlmostEqual(angle, 100, delta=0.1)
ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
self.assertTrue(ff)
ff.UFFAddAngleConstraint(1, 3, 6, False, -10.0, 10.0, 100.0)
r = ff.Minimize()
self.assertTrue(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.assertAlmostEqual(angle, 10, delta=0.1)
def sp2_indices(mol):
"""
Determine which atoms in the rdkit-mol object are sp2 hybridized
by probing for the following criteria:
1) is the atom bounded by 3 neighbors
2) is the angle to all neighbors between 109 and 145 degrees
input: rdkit molecule object
returns: list of atomic indices being sp2-hybridized
"""
sp2_index = []
atoms = mol.GetAtoms()
bonded = []
for bond in mol.GetAtoms()[0].GetBonds():
bonded.append(bond.GetEndAtomIdx())
for atom in atoms:
neighbors = atom.GetNeighbors()
if len(neighbors) == 3:
for a, b in ((0, 1), (1, 2), (2, 0)):
angle = rdMolTransforms.GetAngleDeg(mol.GetConformer(),
bonded[a],
0,
bonded[b])
if (angle > 109 and angle < 145):
sp2_index.append(atom.GetIdx())
return list(set(sp2_index))
def testGetSetAngle(self):
file = os.path.join(RDConfig.RDBaseDir, 'Code', 'GraphMol',
'MolTransforms', 'test_data',
'3-cyclohexylpyridine.mol')
m = Chem.MolFromMolFile(file, True, False)
conf = m.GetConformer()
angle = rdmt.GetAngleDeg(conf, 0, 19, 21)
self.failUnlessAlmostEqual(angle, 109.7, 1)
rdmt.SetAngleDeg(conf, 0, 19, 21, 125.0)
angle = rdmt.GetAngleDeg(conf, 0, 19, 21)
self.failUnlessAlmostEqual(angle, 125.0, 1)
rdmt.SetAngleRad(conf, 21, 19, 0, math.pi / 2.)
angle = rdmt.GetAngleRad(conf, 0, 19, 21)
self.failUnlessAlmostEqual(angle, math.pi / 2., 1)
angle = rdmt.GetAngleDeg(conf, 0, 19, 21)
self.failUnlessAlmostEqual(angle, 90.0, 1)
def testUFFAngleConstraints(self):
m = Chem.MolFromMolBlock(self.molB, True, False)
ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
self.failUnless(ff)
ff.UFFAddAngleConstraint(1, 3, 6, False, 90.0, 90.0, 1.0e5)
r = ff.Minimize()
self.failUnless(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.failUnless(int(angle) == 90)
ff = ChemicalForceFields.UFFGetMoleculeForceField(m)
self.failUnless(ff)
ff.UFFAddAngleConstraint(1, 3, 6, True, -10.0, 10.0, 1.0e5)
r = ff.Minimize()
self.failUnless(r == 0)
conf = m.GetConformer()
angle = rdMolTransforms.GetAngleDeg(conf, 1, 3, 6)
self.failUnless(int(angle) == 100)
def test_measure_angles(acetone):
"""
Make sure we can correctly measure all of the angles in the molecule.
"""
angle_values = acetone.measure_angles()
rdkit_mol = acetone.to_rdkit()
for angle, value in angle_values.items():
assert (pytest.approx(
rdMolTransforms.GetAngleDeg(rdkit_mol.GetConformer(),
*angle)) == value)
def get_angs(f, atid=None): #rdkit
mol = Chem.MolFromMolFile(f, removeHs=False, sanitize=False)
c = mol.GetConformer()
if atid == None:
atid = enumerateAngles(f)
angs = []
for i in range(len(atid)):
m = mol.GetAtomWithIdx(atid[i][1])
if m.GetHybridization() != Chem.HybridizationType.SP:
angs.append(rdt.GetAngleDeg(c, atid[i][0], atid[i][1], atid[i][2]))
return np.array(angs), atid
def smiles_tors():
# Given a pdb file, translate into Smiles string (with possible given starting atom)
# and generate a list of rotatable bonds. Rotatable bond list is written to CHARMM
# stream files (mc_add.str, mc_delete.str) that are used by the MC module used by EnzyDock.
# A crucial assumption is that the rotatable bonds are written in an "outwards" manner
# when covalent docking is done (otherwise CHARMM could rotate protein and not ligand!)
pdb_file = sys.argv[1]
pdb_file = pdb_file.lower() # CHARMM sends in upper case parameters, change to lower
print("Parsing ligand file: ",pdb_file)
mcfile1 = "../stream/mc/mc_add.str"
mcfile2 = "../stream/mc/mc_delete.str"
# Write the mc_add.str file for EnzyDock
file = open(mcfile1,"w")
print_part1(file)
print("Writing file: ", mcfile1)
try:
mol_pdb = Chem.MolFromPDBFile(pdb_file)
num_atoms = mol_pdb.GetNumAtoms(onlyExplicit=True)
except:
print("Error in RDKit read of ligand pdb file %s ..." % pdb_file)
print("Stopping EnzyDock ...\n")
file.write("\nstop\n")
print("Number of ligand atoms: ",num_atoms)
idx = -1
# Find atom that serves as seed (covalently bonded)
if len(sys.argv) > 2:
for i in range(num_atoms):
atom = mol_pdb.GetAtomWithIdx(i)
# print(atom.GetPDBResidueInfo().GetName().strip())
if (atom.GetPDBResidueInfo().GetName().strip() == sys.argv[2]):
idx = atom.GetIdx()
smiles = Chem.MolToSmiles(mol_pdb,True,False,idx)
print("Ligand Smiles: ",smiles)
map = mol_pdb.GetProp('_smilesAtomOutputOrder')
atomorder = [int(i) for i in map.replace('[','').replace(']','').split(',') if i != '''''']
orderarray = np.array(atomorder)
indx_array = np.empty(num_atoms) # index array
for i in range(num_atoms):
indx = int(orderarray[i])
# print(i,indx,mol_pdb.GetAtomWithIdx(indx).GetPDBResidueInfo().GetName())
indx_array[i] = indx
mol = Chem.MolFromSmiles(smiles)
rot_atom_pairs = mol.GetSubstructMatches(RotatableBondSmarts)
print(rot_atom_pairs)
ntors = len(rot_atom_pairs)
k = 0
for i in range(len(rot_atom_pairs)):
indx1 = int(indx_array[ rot_atom_pairs[i][0] ])
indx2 = int(indx_array[ rot_atom_pairs[i][1] ])
atom1 = mol_pdb.GetAtomWithIdx(indx1).GetPDBResidueInfo().GetName()
atom2 = mol_pdb.GetAtomWithIdx(indx2).GetPDBResidueInfo().GetName()
iatom1 = mol_pdb.GetAtomWithIdx(indx1)
iatom2 = mol_pdb.GetAtomWithIdx(indx2)
#print(atom1, atom2, iatom1, iatom2)
conf=mol_pdb.GetConformer(0)
# Check if any angle is linear (torsion not defined). Using 10 degrees as cutoff.
tors_flag = True
for nn in iatom1.GetNeighbors():
indx3 = nn.GetIdx()
if (indx3 != indx2):
angle = rdMolTransforms.GetAngleDeg(conf,indx3, indx1, indx2)
#print(i, indx1, indx2, indx3, angle)
if (abs(180.0 - abs(angle)) < 10.0):
tors_flag = False
for nn in iatom2.GetNeighbors():
indx3 = nn.GetIdx()
if (indx3 != indx1):
angle = rdMolTransforms.GetAngleDeg(conf,indx1, indx2, indx3)
#print(i, indx1, indx2, indx3, angle)
if (abs(180.0 - abs(angle)) < 10.0):
tors_flag = False
if (tors_flag):
j = k + 3
line = "move add mvtp tors weight 1.00 dmax 180.0 label tr" + str(j) + " fewer 0 sele atom ligand_@currligand 1 " \
+ str(atom1) + " show end -\n"
file.write(line)
line = " sele atom ligand_@currligand 1 " \
+ str(atom2) + " show end\n"
file.write(line)
k += 1
else:
ntors -= 1
line = "\nincr ntors by " + str(ntors) + "\n\n"
file.write(line)
print_part2(file)
file.close()
# Write the mc_delete.str file for EnzyDock
file = open(mcfile2,"w")
print("Writing file: ", mcfile2)
print_part3(file)
for i in range(ntors):
j = i + 3
line = "move dele label tr" + str(j) + "\n"
file.write(line)
line = "decr ntors by " + str(ntors) + "\n"
file.write(line)
print_part4(file)
file.close()
# print(Chem.MolToMolBlock(mol_pdb))
# print(Chem.MolToMolBlock(mol))
map = mol_pdb.GetProp('_smilesAtomOutputOrder')
atomorder = [int(i) for i in map.replace('[','').replace(']','').split(',') if i != '''''']
orderarray = np.array(atomorder)
for i in range(num_atoms):
indx = int(orderarray[i])
def exp_rules_output(mol, args, log):
if args.exp_rules == 'Ir_bidentate_x3':
passing = True
ligand_links = []
atom_indexes = []
for atom in mol.GetAtoms():
# Finds the Ir atom and gets the atom types and indexes of all its neighbours
if atom.GetSymbol() in args.metal:
atomic_number = possible_atoms.index(atom.GetSymbol())
atom.SetAtomicNum(atomic_number)
for atom in mol.GetAtoms():
if atom.GetAtomicNum() == atomic_number:
metal_idx = atom.GetIdx()
for x in atom.GetNeighbors():
ligand_links.append(x.GetSymbol())
atom_indexes.append(x.GetIdx())
# I need to get the only 3D conformer generated in that mol object for rdMolTransforms
mol_conf = mol.GetConformer(0)
# This part will identify the pairs of C and N atoms that are part of the same Ph_Py ligand.
# The shape of the atom pairs is '[[C1_ATOM_NUMBER, N1_ATOM_NUMBER],[C2, N2],...]'.
# This information is required for the subsequent filtering process based on angles
if len(atom_indexes) == args.complex_coord[0]:
ligand_atoms = []
for i, _ in enumerate(atom_indexes):
# This is a filter that excludes molecules that fell apart during DFT geometry
# optimization (i.e. a N atom from one of the ligands separated from Ir). The
# max distance allowed can be tuned in length_filter
bond_length = rdMolTransforms.GetBondLength(
mol_conf, metal_idx, atom_indexes[i])
if ligand_links[i] == 'P':
length_filter = 2.60
else:
length_filter = 2.25
if bond_length > length_filter:
passing = False
break
for j, _ in enumerate(atom_indexes):
# Avoid combinations of the same atom with itself
if atom_indexes[i] != atom_indexes[j]:
# We know that the ligands never have 2 carbon atoms bonding the Ir atom. We
# only use atom_indexes[i] for C atoms, and atom_indexes[j] for the potential
# N atoms that are part of the same Ph_Py ligand
if ligand_links[i] == 'C':
# This part detects the Ir-C bond and breaks it, breaking the Ph_Py ring
bond = mol.GetBondBetweenAtoms(
atom_indexes[i], metal_idx)
new_mol = Chem.FragmentOnBonds(
mol, [bond.GetIdx()],
addDummies=True,
dummyLabels=[(atom_indexes[i], metal_idx)])
if new_mol.GetAtomWithIdx(
atom_indexes[i]).IsInRingSize(5):
five_mem = True
else:
five_mem = False
# identify whether or not the initial 5-membered ring formed between [-Ir-C-C-C-N-] is broken when we break the Ir-C bond. This works
# because Ph_Py units bind Ir in the same way always, through 1 C and 1 N that are in the same position, forming a 5-membered ring.
# If this ring is broken, atom_indexes[j] will not be part of a 5-membered ring (atom.IsInRingSize(5) == False) which means that
# this atom was initially inside the same ligand as the parent C of atom_indexes[i])
if not five_mem:
if not new_mol.GetAtomWithIdx(
atom_indexes[j]).IsInRingSize(5):
bond_2 = mol.GetBondBetweenAtoms(
atom_indexes[j], metal_idx)
new_mol_2 = Chem.FragmentOnBonds(
mol, [bond_2.GetIdx()],
addDummies=True,
dummyLabels=[(atom_indexes[j],
metal_idx)])
#doing backwards as well eg. Ir N bond
if not new_mol_2.GetAtomWithIdx(
atom_indexes[i]).IsInRingSize(5):
ligand_atoms.append(
[atom_indexes[i], atom_indexes[j]])
break
else:
if not new_mol.GetAtomWithIdx(
atom_indexes[j]).IsInRingSize(5):
if mol.GetAtomWithIdx(
atom_indexes[j]).IsInRingSize(5):
ligand_atoms.append(
[atom_indexes[i], atom_indexes[j]])
break
if passing:
# This stop variable and the breaks inside the inner loops will break the nested loop if there
# is one angle that does not meet the criteria for valid conformers
stop = False
# For complexes with 3 Ph_Py ligands:
if len(ligand_atoms) == 3:
for i, _ in enumerate(ligand_atoms):
if not stop:
for j, _ in enumerate(ligand_atoms):
# the i<=j part avoids repeating atoms, the i != j part avoid angles
# containing the same number twice (i.e. 4-16-4, this angle will fail)
if i <= j and i != j:
# Calculate the angle between 2 N atoms from different Ph_Py ligands.
# When there are 3 Ph_Py ligands, no 2 N atoms must be in 180 degrees
angle = rdMolTransforms.GetAngleDeg(
mol_conf, ligand_atoms[i][1],
metal_idx, ligand_atoms[j][1])
if (180 - args.angle_off) <= angle <= (
180 + args.angle_off):
passing = False
break
# For complexes with 2 Ph_Py ligands + 1 ligand that is not Ph_Py
if len(ligand_atoms) == 2:
# Since there are only 2 N atoms, we do not need to include a nested loop
angle = rdMolTransforms.GetAngleDeg(
mol_conf, ligand_atoms[0][1], metal_idx,
ligand_atoms[1][1])
# Calculate the angle between 2 N atoms from different Ph_Py ligands.
# When there are 2 Ph_Py ligands, the 2 N atoms from the 2 Ph_Py ligands must be in 180 degrees
if (180 - args.angle_off) <= angle <= (180 +
args.angle_off):
pass
else:
passing = False
# it filters off molecules that the SDF only detects 5 Ir neighbours
else:
passing = False
return passing
