def test_isomer_scoring_function_penalizes_incorrect_number_atoms():
c11h24_arithmetic = IsomerScoringFunction('C12H24',
mean_function='arithmetic')
c11h24_geometric = IsomerScoringFunction('C12H24',
mean_function='geometric')
# all those smiles fit the formula C11H24O
smiles1 = 'CCCCCCCCOCCC'
smiles2 = 'CC(CCOC)CCCCCC'
smiles3 = 'COCCCC(CC(C)CC)C'
# the penalty corresponds to a deviation of 1.0 from the gaussian modifier in the number of C atoms
c_score = GaussianModifier(mu=0, sigma=1)(1.0)
n_atoms_score = 1.0
h_score = 1.0
expected_score_arithmetic = (n_atoms_score + c_score + h_score) / 3.0
expected_score_geometric = (n_atoms_score * c_score * h_score)**(1 / 3)
assert c11h24_arithmetic.score(smiles1) == pytest.approx(
expected_score_arithmetic)
assert c11h24_arithmetic.score(smiles2) == pytest.approx(
expected_score_arithmetic)
assert c11h24_arithmetic.score(smiles3) == pytest.approx(
expected_score_arithmetic)
assert c11h24_geometric.score(smiles1) == pytest.approx(
expected_score_geometric)
assert c11h24_geometric.score(smiles2) == pytest.approx(
expected_score_geometric)
assert c11h24_geometric.score(smiles3) == pytest.approx(
expected_score_geometric)
def test_isomer_scoring_function_returns_one_for_correct_molecule():
c11h24 = IsomerScoringFunction('C11H24')
# all those smiles fit the formula C11H24
smiles1 = 'CCCCCCCCCCC'
smiles2 = 'CC(CCC)CCCCCC'
smiles3 = 'CCCCC(CC(C)CC)C'
assert c11h24.score(smiles1) == 1.0
assert c11h24.score(smiles2) == 1.0
assert c11h24.score(smiles3) == 1.0
def test_isomer_scoring_function_penalizes_incorrect_number_atoms():
c11h24 = IsomerScoringFunction('C12H24')
# all those smiles fit the formula C11H24O
smiles1 = 'CCCCCCCCOCCC'
smiles2 = 'CC(CCOC)CCCCCC'
smiles3 = 'COCCCC(CC(C)CC)C'
# the penalty corresponds to a deviation of 1.0 from the gaussian modifier in the number of C atoms
penalty_tot_num_atoms = 1.0 - GaussianModifier(mu=0, sigma=1)(1.0)
expected_score = 1.0 - penalty_tot_num_atoms / 3.0
assert c11h24.score(smiles1) == pytest.approx(expected_score)
assert c11h24.score(smiles2) == pytest.approx(expected_score)
assert c11h24.score(smiles3) == pytest.approx(expected_score)
def sitagliptin_replacement() -> GoalDirectedBenchmark:
# Find a molecule dissimilar to sitagliptin, but with the same properties
smiles = "Fc1cc(c(F)cc1F)CC(N)CC(=O)N3Cc2nnc(n2CC3)C(F)(F)F"
sitagliptin = Chem.MolFromSmiles(smiles)
target_logp = logP(sitagliptin)
target_tpsa = tpsa(sitagliptin)
similarity = TanimotoScoringFunction(smiles,
fp_type="ECFP4",
score_modifier=GaussianModifier(
mu=0, sigma=0.1))
lp = RdkitScoringFunction(descriptor=logP,
score_modifier=GaussianModifier(mu=target_logp,
sigma=0.2))
tp = RdkitScoringFunction(descriptor=tpsa,
score_modifier=GaussianModifier(mu=target_tpsa,
sigma=5))
isomers = IsomerScoringFunction("C16H15F6N5O")
specification = uniform_specification(1, 10, 100)
return GoalDirectedBenchmark(
name="Sitagliptin MPO",
objective=GeometricMeanScoringFunction([similarity, lp, tp, isomers]),
contribution_specification=specification,
)
def isomers_c7h8n2o2() -> GoalDirectedBenchmark:
"""
Benchmark to try and get 100 isomers for C7H8N2O2.
"""
specification = uniform_specification(100)
return GoalDirectedBenchmark(name='C7H8N2O2',
objective=IsomerScoringFunction('C7H8N2O2'),
contribution_specification=specification)
def zaleplon_with_other_formula() -> GoalDirectedBenchmark:
# zaleplon_with_other_formula with other formula
zaleplon = TanimotoScoringFunction('O=C(C)N(CC)C1=CC=CC(C2=CC=NC3=C(C=NN23)C#N)=C1',
fp_type='ECFP4')
formula = IsomerScoringFunction('C19H17N3O2')
specification = uniform_specification(1, 10, 100)
return GoalDirectedBenchmark(name='Zaleplon MPO',
objective=GeometricMeanScoringFunction([zaleplon, formula]),
contribution_specification=specification)
def isomers_c9h10n2o2pf2cl() -> GoalDirectedBenchmark:
"""
Benchmark to try and get 100 isomers for C9H10N2O2PF2Cl.
"""
specification = uniform_specification(100)
return GoalDirectedBenchmark(
name='C9H10N2O2PF2Cl',
objective=IsomerScoringFunction('C9H10N2O2PF2Cl'),
contribution_specification=specification)
def isomers_c11h24() -> GoalDirectedBenchmark:
"""
Benchmark to try and get all C11H24 molecules there are.
There should be 159 if one ignores stereochemistry.
"""
specification = uniform_specification(159)
return GoalDirectedBenchmark(name='C11H24',
objective=IsomerScoringFunction('C11H24'),
contribution_specification=specification)
def isomers_c9h10n2o2pf2cl(mean_function='geometric', n_samples=250) -> GoalDirectedBenchmark:
"""
Benchmark to try and get 100 isomers for C9H10N2O2PF2Cl.
Args:
mean_function: 'arithmetic' or 'geometric'
"""
specification = uniform_specification(n_samples)
return GoalDirectedBenchmark(name='C9H10N2O2PF2Cl',
objective=IsomerScoringFunction('C9H10N2O2PF2Cl', mean_function=mean_function),
contribution_specification=specification)
def isomers_c7h8n2o2(mean_function='geometric') -> GoalDirectedBenchmark:
"""
Benchmark to try and get 100 isomers for C7H8N2O2.
Args:
mean_function: 'arithmetic' or 'geometric'
"""
specification = uniform_specification(100)
return GoalDirectedBenchmark(name='C7H8N2O2',
objective=IsomerScoringFunction('C7H8N2O2', mean_function=mean_function),
contribution_specification=specification)
def isomers_c11h24(mean_function='geometric') -> GoalDirectedBenchmark:
"""
Benchmark to try and get all C11H24 molecules there are.
There should be 159 if one ignores stereochemistry.
Args:
mean_function: 'arithmetic' or 'geometric'
"""
specification = uniform_specification(159)
return GoalDirectedBenchmark(name='C11H24',
objective=IsomerScoringFunction('C11H24', mean_function=mean_function),
contribution_specification=specification)
def test_isomer_scoring_function_returns_one_for_correct_molecule():
c11h24_arithmetic = IsomerScoringFunction('C11H24',
mean_function='arithmetic')
c11h24_geometric = IsomerScoringFunction('C11H24',
mean_function='geometric')
# all those smiles fit the formula C11H24
smiles1 = 'CCCCCCCCCCC'
smiles2 = 'CC(CCC)CCCCCC'
smiles3 = 'CCCCC(CC(C)CC)C'
assert c11h24_arithmetic.score(smiles1) == 1.0
assert c11h24_arithmetic.score(smiles2) == 1.0
assert c11h24_arithmetic.score(smiles3) == 1.0
assert c11h24_geometric.score(smiles1) == 1.0
assert c11h24_geometric.score(smiles2) == 1.0
assert c11h24_geometric.score(smiles3) == 1.0
def test_isomer_scoring_function_uses_geometric_mean_by_default():
scoring_function = IsomerScoringFunction('C2H4')
assert scoring_function.mean_function == geometric_mean
def test_isomer_scoring_function_invalid_molecule():
sf = IsomerScoringFunction('C60')
assert sf.score('CCCinvalid') == sf.corrupt_score
