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Lig loader minor fix #77

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Lig loader minor fix #77

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aabcecb
rascalMCES increase maxBondMatchPairs
OleinikovasV Oct 16, 2024
0b5823c
feat: skip PlinderSystem ligand 3d confgen
OleinikovasV Oct 16, 2024
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3 changes: 3 additions & 0 deletions src/plinder/core/index/system.py
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Original file line number Diff line number Diff line change
Expand Up @@ -44,9 +44,11 @@ def __init__(
*,
system_id: str,
prune: bool = True,
skip_3d_confgen: bool = False,
) -> None:
self.system_id: str = system_id
self.prune: bool = prune
self.skip_3d_confgen: bool = skip_3d_confgen
self._entry: dict[str, Any] | None = None
self._system: dict[str, Any] | None = None
self._archive: Path | None = None
Expand Down Expand Up @@ -413,6 +415,7 @@ def holo_structure(self) -> Structure:
protein_sequence=self.sequences,
ligand_sdfs=self.ligand_sdfs,
ligand_smiles=self.smiles,
skip_3d_confgen=self.skip_3d_confgen,
structure_type="holo",
)

Expand Down
83 changes: 45 additions & 38 deletions src/plinder/core/structure/atoms.py
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Original file line number Diff line number Diff line change
Expand Up @@ -102,58 +102,64 @@ def atom_array_from_cif_file(


def generate_input_conformer(
template_mol: Chem.Mol, addHs: bool = False, minimize_maxIters: int = -1
template_mol: Chem.Mol,
addHs: bool = False,
minimize_maxIters: int = -1,
skip_3d_confgen: bool = False,
) -> Chem.Mol:
_mol = copy.deepcopy(template_mol)
# need to add Hs to generate sensible conformers
_mol = Chem.AddHs(_mol)
# ps = AllChem.ETKDGv2()
# try embedding molecule using ETKDGv2 (default)
confid = AllChem.EmbedMolecule(
_mol,
# ps,
useRandomCoords=True,
useBasicKnowledge=True,
maxAttempts=100,
randomSeed=42,
)
if confid != -1:
if minimize_maxIters > 0:
# molecule successfully embedded - minimize
success = AllChem.MMFFOptimizeMolecule(_mol, maxIters=minimize_maxIters)
# 0 if the optimization converged,
# -1 if the forcefield could not be set up,
# 1 if more iterations are required.
if success == 1:
log.info(
f"generate_conformer: MMFFOptimizeMolecule - more iterations are required, doubling the steps (2x {minimize_maxIters})"
)
# extend optimization to double the steps (extends by the same amount)
AllChem.MMFFOptimizeMolecule(_mol, maxIters=minimize_maxIters)
elif success == -1:
log.warning(
"generate_conformer: MMFFOptimizeMolecule - the forcefield could not be set up"
)

if skip_3d_confgen:
confid = -1
else:
# this means EmbedMolecule failed
log.warning(
"generate_conformer: default EmbedMolecule - failed, try using useBasicKnowledge=False"
)
# try less optimal approach
# try embedding molecule using ETKDGv2 (default)
confid = AllChem.EmbedMolecule(
_mol,
# ps,
useRandomCoords=True,
useBasicKnowledge=False,
useBasicKnowledge=True,
maxAttempts=100,
randomSeed=42,
)
if confid == -1:
# if that still fails - try generating just 2D conformer
if confid != -1:
if minimize_maxIters > 0:
# molecule successfully embedded - minimize
success = AllChem.MMFFOptimizeMolecule(_mol, maxIters=minimize_maxIters)
# 0 if the optimization converged,
# -1 if the forcefield could not be set up,
# 1 if more iterations are required.
if success == 1:
log.info(
f"generate_conformer: MMFFOptimizeMolecule - more iterations are required, doubling the steps (2x {minimize_maxIters})"
)
# extend optimization to double the steps (extends by the same amount)
AllChem.MMFFOptimizeMolecule(_mol, maxIters=minimize_maxIters)
elif success == -1:
log.warning(
"generate_conformer: MMFFOptimizeMolecule - the forcefield could not be set up"
)
else:
# this means EmbedMolecule failed
log.warning(
"generate_conformer: EmbedMolecule - failed, trying rdDepictor.Compute2DCoords instead"
"generate_conformer: default EmbedMolecule - failed, trying using useBasicKnowledge=False"
)
# try less optimal approach
confid = AllChem.EmbedMolecule(
_mol,
useRandomCoords=True,
useBasicKnowledge=False,
maxAttempts=100,
randomSeed=42,
)
confid = rdDepictor.Compute2DCoords(_mol)

if confid == -1:
# if 3D confgen fails or skipped
log.warning(
"generate_conformer: using 2D (rdDepictor.Compute2DCoords) instead 3D"
)
confid = rdDepictor.Compute2DCoords(_mol)

# verify that mol has conformers
if _mol.GetNumConformers() == 0:
Expand Down Expand Up @@ -198,6 +204,7 @@ def get_template_to_mol_matches(
rascal_opts.returnEmptyMCES = True
rascal_opts.completeAromaticRings = False
rascal_opts.ringMatchesRingOnly = False
rascal_opts.maxBondMatchPairs = 5000
rascal_opts.timeout = 20

results = rdRascalMCES.FindMCES(mol, template, rascal_opts)
Expand Down
12 changes: 11 additions & 1 deletion src/plinder/core/structure/structure.py
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Original file line number Diff line number Diff line change
Expand Up @@ -111,6 +111,7 @@ class Structure(BaseModel):
| None
) = None
add_ligand_hydrogens: bool = False
skip_3d_confgen: bool = False
structure_type: str = "holo"

"""Initialize structure.
Expand Down Expand Up @@ -147,6 +148,8 @@ class Structure(BaseModel):
paired stacked arrays (template vs holo) mapping atom order by index
add_ligand_hydrogens : bool = False
Whether to add hydrogen to ligand or not
skip_3d_confgen : bool = False
Use 2D coords instead of (default) 3D conformer generation
structure_type : str = "holo"
Structure type, "holo", "apo" or "pred"
"""
Expand Down Expand Up @@ -223,7 +226,9 @@ def load_ligands(self) -> None:

# get input_conformer with matches
(template_mol_conformer) = generate_input_conformer(
template_mol, addHs=self.add_ligand_hydrogens
template_mol,
addHs=self.add_ligand_hydrogens,
skip_3d_confgen=self.skip_3d_confgen,
)

self.ligand_mols[name] = (
Expand Down Expand Up @@ -256,6 +261,7 @@ def __add__(self, other: Structure) -> Structure | None:
protein_atom_array=combined_arr,
ligand_mols=self.ligand_mols,
add_ligand_hydrogens=self.add_ligand_hydrogens,
skip_3d_confgen=self.skip_3d_confgen,
structure_type=structure_type,
)
else:
Expand Down Expand Up @@ -303,6 +309,7 @@ def filter(
protein_atom_array=arr,
ligand_mols=self.ligand_mols,
add_ligand_hydrogens=self.add_ligand_hydrogens,
skip_3d_confgen=self.skip_3d_confgen,
structure_type=self.structure_type,
)
assert self.protein_atom_array is not None
Expand Down Expand Up @@ -369,6 +376,7 @@ def align_common_sequence(
protein_atom_array=target_at,
ligand_mols=self.ligand_mols,
add_ligand_hydrogens=self.add_ligand_hydrogens,
skip_3d_confgen=self.skip_3d_confgen,
structure_type=self.structure_type,
)

Expand All @@ -381,6 +389,7 @@ def align_common_sequence(
protein_atom_array=ref_at,
ligand_mols=other.ligand_mols,
add_ligand_hydrogens=other.add_ligand_hydrogens,
skip_3d_confgen=other.skip_3d_confgen,
structure_type=other.structure_type,
)

Expand Down Expand Up @@ -435,6 +444,7 @@ def superimpose(
protein_atom_array=superimposed,
ligand_mols=None if strip_ligands else self.ligand_mols,
add_ligand_hydrogens=self.add_ligand_hydrogens,
skip_3d_confgen=self.skip_3d_confgen,
structure_type=self.structure_type,
),
raw_rmsd,
Expand Down
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