papyrus-structure-pipeline 0.0.5

Papyrus Structure Pipeline

Papyrus Structure Pipeline

Papyrus protocols used to standardize molecules. First used in Papyrus 05.6 .

Installation

From source:

git clone https://github.com/OlivierBeq/Papyrus_Structure_Pipeline.git
pip install ./Papyrus_Structure_Pipeline

with pip:

pip install papyrus-structure-pipeline

Usage

Standardize a compound

Comparison to the ChEMBL Structure Pipeline:

from rdkit import Chem
from chembl_structure_pipeline import standardizer as ChEMBL_standardizer
from papyrus_structure_pipeline import standardizer as Papyrus_standardizer

# CHEMBL1560279
smiles = "CCN(CC)C(=O)[n+]1ccc(OC)cc1.c1ccc([B-](c2ccccc2)(c2ccccc2)c2ccccc2)cc1"

mol = Chem.MolFromSmiles(smiles)
out1 = ChEMBL_standardizer.standardize_mol(mol)
out2 = Papyrus_standardizer.standardize(mol)


print(Chem.MolToSmiles(out1))
# CCN(CC)C(=O)[n+]1ccc(OC)cc1.c1ccc([B-](c2ccccc2)(c2ccccc2)c2ccccc2)cc1

print(Chem.MolToSmiles(out2))
# CCN(CC)C(=O)[n+]1ccc(OC)cc1

Get details on the standardization to identify why it fails for some molecules:

smiles_list = [
    # erlotinib
    "n1cnc(c2cc(c(cc12)OCCOC)OCCOC)Nc1cc(ccc1)C#C",
    # midecamycin
    "CCC(=O)O[C@@H]1CC(=O)O[C@@H](C/C=C/C=C/[C@@H]([C@@H](C[C@@H]([C@@H]([C@H]1OC)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)OC(=O)CC)(C)O)N(C)C)O)CC=O)C)O)C",
    # selenofolate
    "C1=CC(=CC=C1C(=O)NC(CCC(=O)OCC[Se]C#N)C(=O)O)NCC2=CN=C3C(=N2)C(=O)NC(=N3)N",
    # cisplatin
    "N.N.Cl[Pt]Cl"
]

for smiles in smiles_list:
    mol = Chem.MolFromSmiles(smiles)
    print(Papyrus_standardizer.standardize(mol, return_type=True))

    
# (<rdkit.Chem.rdchem.Mol object at 0x000000946F99B580>, <StandardizationResult.CORRECT_MOLECULE: 1>)
# (None, <StandardizationResult.NON_SMALL_MOLECULE: 2>)
# (None, <StandardizationResult.INORGANIC_MOLECULE: 3>)
# (None, <StandardizationResult.MIXTURE_MOLECULE: 4>)

Allow other atoms to be considered organic:

smiles = "CCN(CC)C(=O)C1=CC=C(S1)C2=C3C=CC(=[N+](C)C)C=C3[Se]C4=C2C=CC(=C4)N(C)C.F[P-](F)(F)(F)(F)F"
mol = Chem.MolFromSmiles(smiles)

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (None, <StandardizationResult.INORGANIC_MOLECULE: 3>)

Papyrus_standardizer.ORGANIC_ATOMS.append('Se')

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (<rdkit.Chem.rdchem.Mol object at 0x0000009F24D15F90>, <StandardizationResult.CORRECT_MOLECULE: 1>)

Papyrus_standardizer.ORGANIC_ATOMS = Papyrus_standardizer.ORGANIC_ATOMS[:-1]

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (None, <StandardizationResult.INORGANIC_MOLECULE: 3>)

Add custom substructures to be removed as salts:

# lomitapide
smiles = "C1CN(CCC1NC(=O)C2=CC=CC=C2C3=CC=C(C=C3)C(F)(F)F)CCCCC4(C5=CC=CC=C5C6=CC=CC=C64)C(=O)NCC(F)(F)F.c1ccccc1"
mol = Chem.MolFromSmiles(smiles)

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (None, <StandardizationResult.MIXTURE_MOLECULE: 4>)

Papyrus_standardizer.SALTS.append('c1ccccc1')

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (<rdkit.Chem.rdchem.Mol object at 0x0000009F24D15F90>, <StandardizationResult.CORRECT_MOLECULE: 1>)

Papyrus_standardizer.SALTS = Papyrus_standardizer.SALTS[:-1]

print(Papyrus_standardizer.standardize(mol, return_type=True))
# (None, <StandardizationResult.MIXTURE_MOLECULE: 4>)

Documentation

def standardize(mol,
                remove_additional_salts=True, remove_additional_metals=True,
                filter_mixtures=True, filter_inorganic=True, filter_non_small_molecule=True,
                canonicalize_tautomer=True, small_molecule_min_mw=200, small_molecule_max_mw=800,
                tautomer_allow_stereo_removal=True, tautomer_max_tautomers=0, return_type=False,
                raise_error=True
                ) -> Chem.Mol:

Parameters

• mol : Chem.Mol
  RDKit molecule object to standardize.
• remove_additional_salts : bool
  Removes a custom set of fragments if present in the molecule object.
• remove_additional_metals : bool
  Removes metal fragments if present in the molecule object.
  Ignored if remove_additional_salts is set to False.
• filter_mixtures : bool
  Return None if the molecule is a mixture.
• filter_inorganic : bool
  Return None if the molecule is inorganic.
• filter_non_small_molecule : bool
  Return None if the molecule is not a small molecule.
• canonicalize_tautomer : bool
  Canonicalize the tautomeric state of the molecule.
• small_molecule_min_mw : float
  Molecular weight under which a molecule is considered too small.
• small_molecule_max_mw : float
  Molecular weight above which a molecule is considered too big.
• tautomer_allow_stereo_removal : bool
  Allow the tautomer search algorithm to remove stereocenters.
• tautomer_max_tautomers : int (< 2 ³²)
  Maximum number of tautomers to consider by the tautomer search algorithm.
• return_type : bool
  Add a StandardizationResult to the return value.
• raise_error : bool Raise an exception upon failure, otherwise return None

---

def is_organic(mol, return_type=False) -> bool:

Return whether the RKDit molecule is organic or not.

• Makes internal use of the variable ORGANIC_ATOMS

Parameters

• mol : Chem.Mol
  RDKit molecule object to check the organic nature of.
• return_type : bool
  Add a InorganicSubtype to the return value.

---

def is_small_molecule(mol,
                      min_molwt=200,
                      max_molwt=800
                      ) -> bool:

Return whether the RKDit molecule has a molecular weight within min_molwt and max_molwt.

Parameters

• mol : Chem.Mol
  RDKit molecule object to check the organic nature of.
• min_molwt : float
  Molecular weight under which a molecule is considered too small.
• max_molwt : float
  Molecular weight above which a molecule is considered too big.

---

def is_mixture(mol) -> bool:

Return whether the RKDit molecule is composed of multiple fragments.

Parameters

• mol : Chem.Mol
  RDKit molecule object to check the organic nature of.

---

def _apply_chembl_standardization(mol) -> Chem.Mol:

Apply the ChEMBL structure standardization pipeline on a RDKit molecule.

• Makes use of both ChEMBL_standardizer.get_parent_mol and ChEMBL_standardizer.standardize_mol.
• Ensures the obtained SMILES can be parsed by the RDKit.

Parameters

• mol : Chem.Mol
  RDKit molecule object to apply the ChEMBL Structure Pipeline to.

---

def _canonicalize_tautomer(mol,
                           allow_stereo_removal=True, max_tautomers=2 ** 32 - 1
                           ) -> Chem.Mol:

Obtain the RDKit canonical tautomer of the given RDKit molecule.

• Makes use of both ChEMBL_standardizer.get_parent_mol and ChEMBL_standardizer.standardize_mol.
• Ensures the obtained SMILES can be parsed by the RDKit.

Parameters

• mol : Chem.Mol
  RDKit molecule object to RDKit canonical tautomer of.
• allow_stereo_removal : bool
  Allow the tautomer search algorithm to remove stereocenters.
• max_tautomers : int (<2 ³²)
  Maximum number of tautomers to consider by the tautomer search algorithm.

---

def _remove_supplementary_salts(mol,
                                include_metals=True, return_type=False
                                ) -> Chem.Mol:

Remove substructures (e.g. salts) not dealt with by the ChEMBL pipeline structure.

The additional substructures are defined by the SALTS variable.

Parameters

• mol : Chem.Mol
  RDKit molecule object from which to remove additional substructures.
• include_metals : bool
  Removes metal fragments if present in the molecule object (defined by the METALS variable).
• return_type : bool
  Add a SaltStrippingResult to the return value.