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Merge pull request #254 from forlilab/bond_break_attribute
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add cycle_break attribute to molsetup Bond
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@diogomart
diogomart authored Jan 13, 2025
2 parents 7f6e27a + c563bf9 commit 4c96099
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Showing 6 changed files with 165 additions and 3 deletions.
6 changes: 6 additions & 0 deletions meeko/macrocycle.py
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Original file line number Diff line number Diff line change
Expand Up @@ -36,6 +36,7 @@ def __init__(
double_bond_penalty: float = DEFAULT_DOUBLE_BOND_PENALTY,
max_breaks: int = DEFAULT_MAX_BREAKS,
allow_break_atype_A: bool = False,
untyped: bool = False,
):
"""
Initialize macrocycle typer.
Expand All @@ -50,13 +51,16 @@ def __init__(
max_breaks: int
allow_break_type_A: bool
Allow breaking bonds involving atoms typed A, default is False.
untyped: bool
Does not use atom typing, any rotatable bond can break
"""
self._min_ring_size = min_ring_size
self._max_ring_size = max_ring_size
# accept also double bonds (if nothing better is found)
self._double_bond_penalty = double_bond_penalty
self.max_breaks = max_breaks
self.allow_break_atype_A = allow_break_atype_A
self.untyped = untyped

self.setup = None
self.breakable_rings = None
Expand Down Expand Up @@ -115,6 +119,8 @@ def _score_bond(self, bond: tuple[int, int]) -> int:
bond = Bond.get_bond_id(bond[0], bond[1])
if not self.setup.bond_info[bond].rotatable:
return -1
if self.untyped:
return 100
atom_idx1, atom_idx2 = bond
for i in (atom_idx1, atom_idx2):
atype = self.setup.get_atom_type(i)
Expand Down
7 changes: 5 additions & 2 deletions meeko/molsetup.py
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Original file line number Diff line number Diff line change
Expand Up @@ -51,6 +51,7 @@
DEFAULT_GRAPH = []

DEFAULT_BOND_ROTATABLE = False
DEFAULT_BOND_BREAKABLE = False

DEFAULT_RING_CLOSURE_BONDS_REMOVED = []
DEFAULT_RING_CLOSURE_PSEUDOS_BY_ATOM = defaultdict
Expand Down Expand Up @@ -278,6 +279,7 @@ class Bond(BaseJSONParsable):
index1: int
index2: int
rotatable: bool = DEFAULT_BOND_ROTATABLE
breakable: bool = DEFAULT_BOND_BREAKABLE

def __post_init__(self):
self.canon_id = self.get_bond_id(self.index1, self.index2)
Expand All @@ -291,6 +293,7 @@ def json_encoder(cls, obj: "Bond") -> Optional[dict[str, Any]]:
"index1": obj.index1,
"index2": obj.index2,
"rotatable": obj.rotatable,
"breakable": obj.breakable,
}
return output_dict

Expand All @@ -304,7 +307,8 @@ def _decode_object(cls, obj: dict[str, Any]):
index1 = obj["index1"]
index2 = obj["index2"]
rotatable = obj["rotatable"]
output_bond = cls(index1, index2, rotatable)
breakable = obj.get("breakable", DEFAULT_BOND_BREAKABLE)
output_bond = cls(index1, index2, rotatable, breakable)
return output_bond
# endregion

Expand All @@ -329,7 +333,6 @@ def get_bond_id(idx1: int, idx2: int):
idx_max = max(idx1, idx2)
return idx_min, idx_max


@dataclass
class Ring(BaseJSONParsable):
ring_id: tuple
Expand Down
10 changes: 9 additions & 1 deletion meeko/preparation.py
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Original file line number Diff line number Diff line change
Expand Up @@ -72,6 +72,7 @@ def __init__(
hydrate=False,
flexible_amides=False,
rigid_macrocycles=False,
untyped_macrocycles=False,
min_ring_size=meeko.macrocycle.DEFAULT_MIN_RING_SIZE,
max_ring_size=meeko.macrocycle.DEFAULT_MAX_RING_SIZE,
keep_chorded_rings=False,
Expand Down Expand Up @@ -127,6 +128,7 @@ def __init__(
self.hydrate = hydrate
self.flexible_amides = flexible_amides
self.rigid_macrocycles = rigid_macrocycles
self.untyped_macrocycles = untyped_macrocycles
self.min_ring_size = min_ring_size
self.max_ring_size = max_ring_size
self.keep_chorded_rings = keep_chorded_rings
Expand Down Expand Up @@ -203,6 +205,7 @@ def __init__(
self.max_ring_size,
self.double_bond_penalty,
allow_break_atype_A=self.macrocycle_allow_A,
untyped=self.untyped_macrocycles,
)
self._water_builder = HydrateMoleculeLegacy()
self._classes_setup = {Chem.rdchem.Mol: RDKitMoleculeSetup}
Expand Down Expand Up @@ -328,7 +331,12 @@ def calc_flex(
setup.flexibility_model = flex_model

# add G pseudo atoms and set CG types
update_closure_atoms(setup, bonds_to_break, glue_pseudo_atoms)
if not self.untyped_macrocycles:
update_closure_atoms(setup, bonds_to_break, glue_pseudo_atoms)

for atom1, atom2 in bonds_to_break:
bond_id = Bond.get_bond_id(atom1, atom2)
setup.bond_info[bond_id].breakable = True

return

Expand Down
15 changes: 15 additions & 0 deletions test/json_serialization_test.py
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Original file line number Diff line number Diff line change
Expand Up @@ -341,6 +341,21 @@ def test_dihedral_equality():
check_molsetup_equality(starting_molsetup, decoded_molsetup)
return


def test_broken_bond():
fn = str(pkgdir / "test" / "macrocycle_data" / "lorlatinib.mol")
mol = Chem.MolFromMolFile(fn, removeHs=False)
mk_prep_untyped = MoleculePreparation(untyped_macrocycles=True)
starting_molsetup = mk_prep_untyped(mol)[0]
decoded_molsetup = RDKitMoleculeSetup.from_json(starting_molsetup.to_json())
count_rotatable = 0
count_breakable = 0
for bond_id, bond_info in decoded_molsetup.bond_info.items():
count_rotatable += bond_info.rotatable
count_breakable += bond_info.breakable
assert count_rotatable == 10
assert count_breakable == 1

# endregion


Expand Down
106 changes: 106 additions & 0 deletions test/macrocycle_data/lorlatinib.mol
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Original file line number Diff line number Diff line change
@@ -0,0 +1,106 @@
_i0
RDKit 3D

49 52 0 0 0 0 0 0 0 0999 V2000
2.0287 0.5847 -2.8580 C 0 0 0 0 0 0 0 0 0 0 0 0
2.5178 1.0230 -1.4775 C 0 0 1 0 0 0 0 0 0 0 0 0
1.8039 2.1855 -1.0050 O 0 0 0 0 0 0 0 0 0 0 0 0
0.7602 1.9598 -0.1565 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.4054 1.3343 -0.5803 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.4241 1.1052 0.3389 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.2623 1.6088 1.6263 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.1633 2.2777 2.0483 N 0 0 0 0 0 0 0 0 0 0 0 0
0.8288 2.4468 1.1546 C 0 0 0 0 0 0 0 0 0 0 0 0
1.9774 3.0843 1.6275 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.5429 0.2554 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.5683 -1.1293 -0.3755 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.4509 -2.1347 -0.5607 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.1849 -1.7343 0.0593 N 0 0 0 0 0 0 0 0 0 0 0 0
-0.1318 -1.7409 1.5196 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9456 -1.6441 -0.7639 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9295 -1.8994 -1.9639 O 0 0 0 0 0 0 0 0 0 0 0 0
2.2456 -1.2536 -0.1647 C 0 0 0 0 0 0 0 0 0 0 0 0
2.8248 -2.2022 0.7057 C 0 0 0 0 0 0 0 0 0 0 0 0
4.0045 -1.9180 1.3883 C 0 0 0 0 0 0 0 0 0 0 0 0
4.6125 -0.6902 1.1947 C 0 0 0 0 0 0 0 0 0 0 0 0
5.7392 -0.3992 1.8571 F 0 0 0 0 0 0 0 0 0 0 0 0
4.0837 0.2356 0.3000 C 0 0 0 0 0 0 0 0 0 0 0 0
2.9075 -0.0357 -0.4407 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.8322 -1.5421 -0.5749 N 0 0 0 0 0 0 0 0 0 0 0 0
-4.5864 -0.4479 -0.3709 N 0 0 0 0 0 0 0 0 0 0 0 0
-6.0209 -0.5372 -0.5309 C 0 0 0 0 0 0 0 0 0 0 0 0
-3.8650 0.6556 -0.0159 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.4316 1.9274 0.2613 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.9252 2.9499 0.4950 N 0 0 0 0 0 0 0 0 0 0 0 0
0.9823 0.2838 -2.8717 H 0 0 0 0 0 0 0 0 0 0 0 0
2.6373 -0.2332 -3.2566 H 0 0 0 0 0 0 0 0 0 0 0 0
2.0917 1.4280 -3.5564 H 0 0 0 0 0 0 0 0 0 0 0 0
3.4903 1.4646 -1.7456 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.5136 0.9899 -1.6014 H 0 0 0 0 0 0 0 0 0 0 0 0
-2.0157 1.4573 2.3952 H 0 0 0 0 0 0 0 0 0 0 0 0
2.2724 3.8074 0.9805 H 0 0 0 0 0 0 0 0 0 0 0 0
1.7720 3.4374 2.5572 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.3265 -2.2962 -1.6370 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.7367 -3.0982 -0.1209 H 0 0 0 0 0 0 0 0 0 0 0 0
0.1176 -2.7534 1.8503 H 0 0 0 0 0 0 0 0 0 0 0 0
0.6194 -1.0400 1.8902 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.1006 -1.4673 1.9447 H 0 0 0 0 0 0 0 0 0 0 0 0
2.3465 -3.1678 0.8574 H 0 0 0 0 0 0 0 0 0 0 0 0
4.4448 -2.6381 2.0701 H 0 0 0 0 0 0 0 0 0 0 0 0
4.6138 1.1780 0.1750 H 0 0 0 0 0 0 0 0 0 0 0 0
-6.2915 -1.5507 -0.8390 H 0 0 0 0 0 0 0 0 0 0 0 0
-6.3284 0.1769 -1.2988 H 0 0 0 0 0 0 0 0 0 0 0 0
-6.4900 -0.3038 0.4282 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 0
3 4 1 0
4 5 1 0
5 6 2 0
6 7 1 0
7 8 2 0
8 9 1 0
9 10 1 0
6 11 1 0
11 12 1 0
12 13 1 0
13 14 1 0
14 15 1 0
14 16 1 0
16 17 2 0
16 18 1 0
18 19 2 0
19 20 1 0
20 21 2 0
21 22 1 0
21 23 1 0
23 24 2 0
12 25 2 0
25 26 1 0
26 27 1 0
26 28 1 0
28 29 1 0
29 30 3 0
24 2 1 0
9 4 2 0
28 11 2 0
24 18 1 0
1 31 1 0
1 32 1 0
1 33 1 0
2 34 1 6
5 35 1 0
7 36 1 0
10 37 1 0
10 38 1 0
13 39 1 0
13 40 1 0
15 41 1 0
15 42 1 0
15 43 1 0
19 44 1 0
20 45 1 0
23 46 1 0
27 47 1 0
27 48 1 0
27 49 1 0
M END
24 changes: 24 additions & 0 deletions test/macrocycle_test.py
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Original file line number Diff line number Diff line change
Expand Up @@ -101,3 +101,27 @@ def test_all():
for molname in num_cycle_breaks:
run(molname)

def test_untyped_macrocycle():
fn = str(workdir / "macrocycle_data" / "lorlatinib.mol")
mol = Chem.MolFromMolFile(fn, removeHs=False)

# type based, can only break C-C bonds, but we have none
mk_prep_typed = MoleculePreparation()
molsetup_typed = mk_prep_typed(mol)[0]
count_rotatable = 0
count_breakable = 0
for bond_id, bond_info in molsetup_typed.bond_info.items():
count_rotatable += bond_info.rotatable
count_breakable += bond_info.breakable
assert count_rotatable == 2
assert count_breakable == 0

mk_prep_untyped = MoleculePreparation(untyped_macrocycles=True)
molsetup_untyped = mk_prep_untyped(mol)[0]
count_rotatable = 0
count_breakable = 0
for bond_id, bond_info in molsetup_untyped.bond_info.items():
count_rotatable += bond_info.rotatable
count_breakable += bond_info.breakable
assert count_rotatable == 10
assert count_breakable == 1

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