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Add private additional substructure functionality and test (#1590)
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* add additional substructure functionality and test

* extend test, don't attempt to fix typing tangle

* fix weird bug where OETKW has to handle a molecule that RDKit made with a stereocenter that OE doesn't think is stereogenic

* black
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@j-wags
j-wags authored Apr 26, 2023
1 parent 110ba6f commit 4085ad8
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2 changes: 1 addition & 1 deletion docs/releasehistory.md
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Expand Up @@ -10,7 +10,7 @@ Releases follow the `major.minor.micro` scheme recommended by [PEP440](https://w

### New features
- [PR #1567](https://github.com/openforcefield/openff-toolkit/pull/1567): Allows setting `Molecule.name` in `Molecule.from_smiles`, `from_inchi`, `from_polymer_pdb`, and `from_pdb_and_smiles`.
- [PR #1565](https://github.com/openforcefield/openff-toolkit/pull/1565): Adds `Topology.from_pdb`
- [PR #1565](https://github.com/openforcefield/openff-toolkit/pull/1565): Adds `Topology.from_pdb`.

### Behavior changes
- [PR #1569](https://github.com/openforcefield/openff-toolkit/pull/1569): Several instances of `Exception` being raised are now replaced with other exceptions being raised.
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78 changes: 78 additions & 0 deletions openff/toolkit/data/proteins/ace-ZZZ-gly-nme.pdb
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@@ -0,0 +1,78 @@
REMARK 1 CREATED WITH OPENMM 8.0, 2023-04-25
ATOM 1 C ACE A 1 -2.066 -2.592 0.175 1.00 0.00 C
ATOM 2 CH3 ACE A 1 -2.551 -3.997 0.367 1.00 0.00 C
ATOM 3 O ACE A 1 -2.742 -1.857 -0.621 1.00 0.00 O
ATOM 4 H1 ACE A 1 -3.605 -4.130 0.022 1.00 0.00 H
ATOM 5 H2 ACE A 1 -1.889 -4.674 -0.185 1.00 0.00 H
ATOM 6 H3 ACE A 1 -2.443 -4.229 1.460 1.00 0.00 H
HETATM 7 C3x ZZZ A 2 0.958 -0.804 0.130 1.00 0.00 C
HETATM 8 O2x ZZZ A 2 1.422 0.410 -0.180 1.00 0.00 O
HETATM 9 P1x ZZZ A 2 2.782 0.984 0.562 1.00 0.00 P
HETATM 10 O3x ZZZ A 2 3.223 2.281 -0.117 1.00 0.00 O
HETATM 11 O4x ZZZ A 2 4.036 -0.203 0.428 1.00 0.00 O
HETATM 12 C4x ZZZ A 2 5.229 0.481 0.703 1.00 0.00 C
HETATM 13 N1x ZZZ A 2 5.451 1.459 -0.299 1.00 0.00 N
HETATM 14 C5x ZZZ A 2 6.447 2.391 0.081 1.00 0.00 C
HETATM 15 O5x ZZZ A 2 7.549 2.337 -0.776 1.00 0.00 O
HETATM 16 O6x ZZZ A 2 2.467 1.269 2.209 1.00 0.00 O
HETATM 17 C6x ZZZ A 2 -0.465 -0.731 0.692 1.00 0.00 C
HETATM 18 H4x ZZZ A 2 1.563 -1.211 0.974 1.00 0.00 H
HETATM 19 C7x ZZZ A 2 0.969 -1.745 -1.031 1.00 0.00 C
HETATM 20 N2x ZZZ A 2 -0.925 -2.088 0.827 1.00 0.00 N
HETATM 21 H5x ZZZ A 2 -0.519 -0.217 1.646 1.00 0.00 H
HETATM 22 C8x ZZZ A 2 -1.233 0.066 -0.254 1.00 0.00 C
HETATM 23 H6x ZZZ A 2 2.010 -1.912 -1.357 1.00 0.00 H
HETATM 24 H7x ZZZ A 2 0.425 -1.369 -1.907 1.00 0.00 H
HETATM 25 H8x ZZZ A 2 0.577 -2.754 -0.739 1.00 0.00 H
HETATM 26 H9x ZZZ A 2 -0.386 -2.741 1.455 1.00 0.00 H
HETATM 27 O7x ZZZ A 2 -0.724 0.367 -1.381 1.00 0.00 O
HETATM 28 H10x ZZZ A 2 5.158 0.829 1.726 1.00 0.00 H
HETATM 29 H11x ZZZ A 2 6.021 -0.306 0.563 1.00 0.00 H
HETATM 30 H12x ZZZ A 2 5.170 1.366 -1.230 1.00 0.00 H
HETATM 31 H13x ZZZ A 2 6.754 2.406 1.128 1.00 0.00 H
HETATM 32 H14x ZZZ A 2 5.983 3.478 -0.107 1.00 0.00 H
HETATM 33 H15x ZZZ A 2 8.354 2.068 -0.209 1.00 0.00 H
ATOM 34 N GLY A 3 -2.558 0.532 -0.002 1.00 0.00 N
ATOM 35 CA GLY A 3 -3.219 1.371 -0.989 1.00 0.00 C
ATOM 36 H GLY A 3 -3.047 0.271 0.916 1.00 0.00 H
ATOM 37 C GLY A 3 -4.631 1.568 -0.767 1.00 0.00 C
ATOM 38 HA1 GLY A 3 -2.631 2.367 -0.989 1.00 0.00 H
ATOM 39 HA2 GLY A 3 -3.015 0.934 -1.970 1.00 0.00 H
ATOM 40 O GLY A 3 -5.267 2.435 -1.509 1.00 0.00 O
ATOM 41 N NME A 4 -5.391 0.878 0.228 1.00 0.00 N
ATOM 42 C NME A 4 -6.816 1.155 0.367 1.00 0.00 C
ATOM 43 H NME A 4 -5.003 0.147 0.835 1.00 0.00 H
ATOM 44 HH31 NME A 4 -7.186 1.620 -0.590 1.00 0.00 H
ATOM 45 HH32 NME A 4 -6.902 1.861 1.199 1.00 0.00 H
ATOM 46 HH33 NME A 4 -7.332 0.226 0.536 1.00 0.00 H
TER 47 NME A 4
CONECT 6 2
CONECT 7 8 17 18 19
CONECT 8 7 9
CONECT 9 8 10 11 16
CONECT 10 9
CONECT 11 9 12
CONECT 12 11 13 28 29
CONECT 13 12 14 30
CONECT 14 13 15 31 32
CONECT 15 14 33
CONECT 16 9
CONECT 17 7 20 21 22
CONECT 18 7
CONECT 19 7 23 24 25
CONECT 20 1 17 26
CONECT 21 17
CONECT 22 17 27 34
CONECT 23 19
CONECT 24 19
CONECT 25 19
CONECT 26 20
CONECT 27 22
CONECT 28 12
CONECT 29 12
CONECT 30 13
CONECT 31 14
CONECT 32 14
CONECT 33 15
CONECT 34 22
END
98 changes: 98 additions & 0 deletions openff/toolkit/data/proteins/ace-ZZZ-gly-nme.sdf
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RDKit 3D

46 45 0 0 0 0 0 0 0 0999 V2000
0.3304 -3.1891 -0.0011 C 0 0 0 0 0 0 0 0 0 0 0 0
0.1741 -4.6801 -0.0964 C 0 0 0 0 0 0 0 0 0 0 0 0
1.2672 -2.5771 -0.5521 O 0 0 0 0 0 0 0 0 0 0 0 0
-0.9097 -4.8221 -0.3619 H 0 0 0 0 0 0 0 0 0 0 0 0
0.3001 -5.0996 0.9179 H 0 0 0 0 0 0 0 0 0 0 0 0
0.8050 -5.1289 -0.8713 H 0 0 0 0 0 0 0 0 0 0 0 0
0.1336 -0.1285 0.2580 C 0 0 1 0 0 0 0 0 0 0 0 0
1.4706 -0.2969 0.4981 O 0 0 0 0 0 0 0 0 0 0 0 0
2.3559 0.7366 -0.5599 P 0 0 2 0 0 5 0 0 0 0 0 0
1.4404 1.3216 -1.6193 O 0 0 0 0 0 0 0 0 0 0 0 0
3.5581 -0.0903 -1.3039 O 0 0 0 0 0 0 0 0 0 0 0 0
4.8210 0.0033 -0.8250 C 0 0 0 0 0 0 0 0 0 0 0 0
5.4547 1.2719 -0.7892 N 0 0 0 0 0 0 0 0 0 0 0 0
6.8337 1.1928 -0.3195 C 0 0 0 0 0 0 0 0 0 0 0 0
7.4169 2.4351 -0.2557 O 0 0 0 0 0 0 0 0 0 0 0 0
2.9095 1.9785 0.4905 O 0 0 0 0 0 1 0 0 0 0 0 0
-0.7328 -1.0893 0.9908 C 0 0 2 0 0 0 0 0 0 0 0 0
-0.1291 1.2859 0.9765 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.1316 0.0777 -0.7485 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.6635 -2.4723 0.7661 N 0 0 0 0 0 0 0 0 0 0 0 0
-2.1195 -0.6056 1.2094 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.2330 -1.0071 2.0751 H 0 0 0 0 0 0 0 0 0 0 0 0
0.0941 1.0204 2.0208 H 0 0 0 0 0 0 0 0 0 0 0 0
0.4747 2.0365 0.5326 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.2269 1.3969 0.8838 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.4060 -3.1368 1.2072 H 0 0 0 0 0 0 0 0 0 0 0 0
-2.4522 -0.1233 2.3086 O 0 0 0 0 0 0 0 0 0 0 0 0
4.8640 -0.4320 0.2332 H 0 0 0 0 0 0 0 0 0 0 0 0
5.4822 -0.7262 -1.3981 H 0 0 0 0 0 0 0 0 0 0 0 0
4.9861 1.9578 -0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0
7.3873 0.6244 -1.1562 H 0 0 0 0 0 0 0 0 0 0 0 0
6.9138 0.5503 0.5556 H 0 0 0 0 0 0 0 0 0 0 0 0
7.0636 2.9092 0.5212 H 0 0 0 0 0 0 0 0 0 0 0 0
-3.0415 -0.7172 0.1714 N 0 0 0 0 0 0 0 0 0 0 0 0
-4.4044 -0.3150 0.1018 C 0 0 0 0 0 0 0 0 0 0 0 0
-2.6396 -1.2160 -0.7218 H 0 0 0 0 0 0 0 0 0 0 0 0
-4.6428 1.1657 0.0527 C 0 0 0 0 0 0 0 0 0 0 0 0
-4.9443 -0.6883 1.0864 H 0 0 0 0 0 0 0 0 0 0 0 0
-4.9708 -0.8216 -0.6749 H 0 0 0 0 0 0 0 0 0 0 0 0
-3.7263 1.9719 0.1167 O 0 0 0 0 0 0 0 0 0 0 0 0
-5.9810 1.5745 -0.0860 N 0 0 0 0 0 0 0 0 0 0 0 0
-6.2972 2.9715 -0.1969 C 0 0 0 0 0 0 0 0 0 0 0 0
-6.7606 0.8731 -0.1164 H 0 0 0 0 0 0 0 0 0 0 0 0
-5.5368 3.5799 0.3512 H 0 0 0 0 0 0 0 0 0 0 0 0
-6.2938 3.2727 -1.2837 H 0 0 0 0 0 0 0 0 0 0 0 0
-7.2938 3.1548 0.2649 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
1 3 2 0
1 20 1 0
2 4 1 0
2 5 1 0
2 6 1 0
7 8 1 0
7 17 1 0
7 18 1 0
7 19 1 6
8 9 1 0
9 10 2 0
9 11 1 0
9 16 1 1
11 12 1 0
12 13 1 0
12 28 1 0
12 29 1 0
13 14 1 0
13 30 1 0
14 15 1 0
14 31 1 0
14 32 1 0
15 33 1 0
17 20 1 0
17 21 1 0
17 22 1 1
18 23 1 0
18 24 1 0
18 25 1 0
20 26 1 0
21 27 2 0
21 34 1 0
34 35 1 0
34 36 1 0
35 37 1 0
35 38 1 0
35 39 1 0
37 40 2 0
37 41 1 0
41 42 1 0
41 43 1 0
42 44 1 0
42 45 1 0
42 46 1 0
M CHG 1 16 -1
M END
$$$$
30 changes: 30 additions & 0 deletions openff/toolkit/tests/test_topology.py
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Expand Up @@ -835,6 +835,36 @@ def test_from_pdb_overlapping_unique_mols(self):
assert po4.is_isomorphic_with(top2.molecule(0))
assert phenylphosphate.is_isomorphic_with(top2.molecule(1))

@requires_rdkit
def test_from_pdb_additional_substructures(self):
"""Test that the _additional_substructures arg is wired up correctly"""
with pytest.raises(UnassignedChemistryInPDBError):
Topology.from_pdb(get_data_file_path("proteins/ace-ZZZ-gly-nme.pdb"))

# Make unnatural AA
mol = Molecule.from_smiles("N[C@@H]([C@@H](C)O[P@](=O)(OCNCO)[O-])C(=O)")
# Get the indices of an N term and C term hydrogen for removal
leaving_atoms = mol.chemical_environment_matches("[H:1]N([H])CC(=O)[H:2]")[0]

# Label the atoms with whether they're leaving
for atom in mol.atoms:
if atom.molecule_atom_index not in leaving_atoms:
atom.metadata["substructure_atom"] = True
else:
atom.metadata["substructure_atom"] = False

top = Topology.from_pdb(
get_data_file_path("proteins/ace-ZZZ-gly-nme.pdb"),
_additional_substructures=[mol],
)

expected_mol = Molecule.from_file(
get_data_file_path("proteins/ace-ZZZ-gly-nme.sdf")
)
assert top.molecule(0).is_isomorphic_with(
expected_mol, atom_stereochemistry_matching=False
)

@requires_pkg("mdtraj")
def test_from_mdtraj(self):
"""Test construction of an OpenFF Topology from an MDTraj Topology object"""
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1 change: 1 addition & 0 deletions openff/toolkit/topology/molecule.py
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Expand Up @@ -3558,6 +3558,7 @@ def chemical_environment_matches(
self,
smirks,
unique=unique,
raise_exception_types=[],
)
elif isinstance(toolkit_registry, ToolkitWrapper):
matches = toolkit_registry.find_smarts_matches( # type: ignore[attr-defined]
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27 changes: 27 additions & 0 deletions openff/toolkit/topology/topology.py
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Expand Up @@ -12,6 +12,7 @@
"""
import itertools
import re
import warnings
from collections import defaultdict
from collections.abc import MutableMapping
Expand Down Expand Up @@ -1535,6 +1536,7 @@ def from_pdb(
file_path: Union[str, TextIO],
unique_molecules: Optional[Iterable[Molecule]] = None,
toolkit_registry=GLOBAL_TOOLKIT_REGISTRY,
_additional_substructures: Optional[Iterable[Molecule]] = None,
):
"""
Loads supported or user-specified molecules from a PDB file.
Expand Down Expand Up @@ -1614,6 +1616,9 @@ def from_pdb(
PDB. See above for details.
toolkit_registry : ToolkitRegistry. Default = None
The ToolkitRegistry to use as the cheminformatics backend.
_additional_substructures : Iterable of Molecule, Default = None
Experimental and unstable. Molecule with atom.metadata["substructure_atom"] =
True or False for all atoms.
Returns
-------
Expand Down Expand Up @@ -1682,6 +1687,28 @@ def from_pdb(
a.name for a in unique_molecule.atoms
]

substructure_dictionary["ADDITIONAL_SUBSTRUCTURE"] = {}

if _additional_substructures:
for mol in _additional_substructures:
label_mol = Molecule(mol)
c = 0
label_mol.properties["atom_map"] = {}
for atom in label_mol.atoms:
if atom.metadata["substructure_atom"]:
label_mol.properties["atom_map"][atom.molecule_atom_index] = c
c += 1
smi = label_mol.to_smiles(mapped=True)
# remove unmapped atoms from mapped smiles. This will catch things like
# `[H]` and `[Cl]` but not anything with 3 characters like `[H:1]`
smi = re.sub("\[[A-Za-z]{1,2}\]", "", smi)
# Remove any orphaned () that remain
smi = smi.replace("()", "")

substructure_dictionary["ADDITIONAL_SUBSTRUCTURE"][smi] = []

substructure_dictionary["ADDITIONAL_SUBSTRUCTURE_OVERLAP"] = {}

coords_angstrom = np.array(
[[*vec3.value_in_unit(openmm_unit.angstrom)] for vec3 in pdb.getPositions()]
)
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44 changes: 22 additions & 22 deletions openff/toolkit/utils/__init__.py
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@@ -1,29 +1,10 @@
from openff.toolkit.utils.utils import (
all_subclasses,
convert_0_1_smirnoff_to_0_2,
convert_0_2_smirnoff_to_0_3,
convert_all_quantities_to_string,
convert_all_strings_to_quantity,
deserialize_numpy,
get_data_file_path,
get_molecule_parameterIDs,
inherit_docstrings,
object_to_quantity,
quantity_to_string,
requires_package,
serialize_numpy,
string_to_quantity,
string_to_unit,
temporary_cd,
unit_to_string,
)
from openff.toolkit.utils.constants import (
DEFAULT_AROMATICITY_MODEL,
ALLOWED_AROMATICITY_MODELS,
DEFAULT_FRACTIONAL_BOND_ORDER_MODEL,
ALLOWED_CHARGE_MODELS,
ALLOWED_FRACTIONAL_BOND_ORDER_MODELS,
DEFAULT_AROMATICITY_MODEL,
DEFAULT_CHARGE_MODEL,
ALLOWED_CHARGE_MODELS,
DEFAULT_FRACTIONAL_BOND_ORDER_MODEL,
)
from openff.toolkit.utils.toolkits import (
AMBERTOOLS_AVAILABLE,
Expand Down Expand Up @@ -53,3 +34,22 @@
ToolkitWrapper,
UndefinedStereochemistryError,
)
from openff.toolkit.utils.utils import (
all_subclasses,
convert_0_1_smirnoff_to_0_2,
convert_0_2_smirnoff_to_0_3,
convert_all_quantities_to_string,
convert_all_strings_to_quantity,
deserialize_numpy,
get_data_file_path,
get_molecule_parameterIDs,
inherit_docstrings,
object_to_quantity,
quantity_to_string,
requires_package,
serialize_numpy,
string_to_quantity,
string_to_unit,
temporary_cd,
unit_to_string,
)
8 changes: 7 additions & 1 deletion openff/toolkit/utils/rdkit_wrapper.py
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Expand Up @@ -407,7 +407,13 @@ def _polymer_openmm_topology_to_rdmol(

# Some special residues are allowed to overlap/override previous matches
if any(m in already_assigned_nodes for m in match) and (
res_name not in ["PEPTIDE_BOND", "DISULFIDE", "UNIQUE_MOLECULE"]
res_name
not in [
"PEPTIDE_BOND",
"DISULFIDE",
"UNIQUE_MOLECULE",
"ADDITIONAL_SUBSTRUCTURE",
]
):
continue
already_assigned_nodes.update(match)
Expand Down

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