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## These MolStandardizer classes are due to Paolo Tosco
## It was taken from the FS-Mol github
## (https://github.com/microsoft/FS-Mol/blob/main/fs_mol/preprocessing/utils/
## standardizer.py)
## They ensure that a sequence of standardization operations are applied
## https://gist.github.com/ptosco/7e6b9ab9cc3e44ba0919060beaed198e
import logging
from rdkit import Chem, RDLogger
from rdkit.Chem.MolStandardize import rdMolStandardize
class BaseLogger:
"""
Simple logging base class.
Inherit from this class and call self.get_logger() to
get a logger bearing the class name.
"""
DEFAULT_LOG_LEVEL = logging.WARNING
def __init__(self):
self._log_level = self.DEFAULT_LOG_LEVEL
def set_log_level(self, log_level):
if not getattr(logging, log_level):
raise TypeError(f"log_level {log_level} does not exist in logging")
self._log_level = log_level
def get_logger(self):
"""Return a logger bearing the class name."""
logger = logging.getLogger(self.__class__.__name__)
if not logger.hasHandlers():
handler = logging.StreamHandler()
formatter = logging.Formatter("[%(asctime)s:%(name)s:%(levelname)s] %(message)s")
handler.setFormatter(formatter)
logger.addHandler(handler)
logger.setLevel(self._log_level)
return logger
class Standardizer(BaseLogger):
"""
Simple wrapper class around rdkit Standardizer.
"""
DEFAULT_CANON_TAUT = False
DEFAULT_METAL_DISCONNECT = False
MAX_TAUTOMERS = 100
MAX_TRANSFORMS = 100
MAX_RESTARTS = 200
PREFER_ORGANIC = True
def __init__(
self,
metal_disconnect=None,
canon_taut=None,
):
"""
Constructor.
All parameters are optional.
:param metal_disconnect: if True, metallorganic complexes are
disconnected
:param canon_taut: if True, molecules are converted to their
canonical tautomer
"""
super().__init__()
if metal_disconnect is None:
metal_disconnect = self.DEFAULT_METAL_DISCONNECT
if canon_taut is None:
canon_taut = self.DEFAULT_CANON_TAUT
self._canon_taut = canon_taut
self._metal_disconnect = metal_disconnect
self._taut_enumerator = None
self._rdlogger = None
self._uncharger = None
self._lfrag_chooser = None
self._metal_disconnector = None
self._normalizer = None
self._reionizer = None
self._params = None
@property
def params(self):
"""Return the MolStandardize CleanupParameters."""
if self._params is None:
self._params = rdMolStandardize.CleanupParameters()
self._params.maxTautomers = self.MAX_TAUTOMERS
self._params.maxTransforms = self.MAX_TRANSFORMS
self._params.maxRestarts = self.MAX_RESTARTS
self._params.preferOrganic = self.PREFER_ORGANIC
self._params.tautomerRemoveSp3Stereo = False
return self._params
@property
def canon_taut(self):
"""Return whether tautomer canonicalization will be done."""
return self._canon_taut
@property
def metal_disconnect(self):
"""Return whether metallorganic complexes will be disconnected."""
return self._metal_disconnect
@property
def taut_enumerator(self):
"""Return the TautomerEnumerator object."""
if self._taut_enumerator is None:
self._taut_enumerator = rdMolStandardize.TautomerEnumerator(self.params)
return self._taut_enumerator
@property
def uncharger(self):
"""Return the Uncharger object."""
if self._uncharger is None:
self._uncharger = rdMolStandardize.Uncharger()
return self._uncharger
@property
def lfrag_chooser(self):
"""Return the LargestFragmentChooser object."""
if self._lfrag_chooser is None:
self._lfrag_chooser = rdMolStandardize.LargestFragmentChooser(self.params.preferOrganic)
return self._lfrag_chooser
@property
def metal_disconnector(self):
"""Return the MetalDisconnector object."""
if self._metal_disconnector is None:
self._metal_disconnector = rdMolStandardize.MetalDisconnector()
return self._metal_disconnector
@property
def normalizer(self):
"""Return the Normalizer object."""
if self._normalizer is None:
self._normalizer = rdMolStandardize.Normalizer(
self.params.normalizationsFile, self.params.maxRestarts
)
return self._normalizer
@property
def reionizer(self):
"""Return the Reionizer object."""
if self._reionizer is None:
self._reionizer = rdMolStandardize.Reionizer(self.params.acidbaseFile)
return self._reionizer
def charge_parent(self, mol_in):
"""Sequentially apply a series of MolStandardize operations:
* MetalDisconnector
* Normalizer
* Reionizer
* LargestFragmentChooser
* Uncharger
The net result is that a desalted, normalized, neutral
molecule with implicit Hs is returned.
"""
params = Chem.RemoveHsParameters()
params.removeAndTrackIsotopes = True
mol_in = Chem.RemoveHs(mol_in, params, sanitize=False)
if self._metal_disconnect:
mol_in = self.metal_disconnector.Disconnect(mol_in)
normalized = self.normalizer.normalize(mol_in)
Chem.SanitizeMol(normalized)
normalized = self.reionizer.reionize(normalized)
Chem.AssignStereochemistry(normalized)
normalized = self.lfrag_chooser.choose(normalized)
normalized = self.uncharger.uncharge(normalized)
# need this to reassess aromaticity on things like
# cyclopentadienyl, tropylium, azolium, etc.
Chem.SanitizeMol(normalized)
return Chem.RemoveHs(Chem.AddHs(normalized))
def standardize_mol(self, mol_in):
"""
Standardize a single molecule.
:param mol_in: a Chem.Mol
:return: * (standardized Chem.Mol, n_taut) tuple
if success. n_taut will be negative if
tautomer enumeration was aborted due
to reaching a limit
* (None, error_msg) if failure
This calls self.charge_parent() and, if self._canon_taut
is True, runs tautomer canonicalization.
"""
logger = self.get_logger()
if self._rdlogger is None:
self._rdlogger = RDLogger.logger()
self._rdlogger.setLevel(RDLogger.CRITICAL)
n_tautomers = 0
if isinstance(mol_in, Chem.Mol):
name = None
try:
name = mol_in.GetProp("_Name")
except KeyError:
pass
if not name:
name = "NONAME"
else:
error = f"Expected SMILES or Chem.Mol as input, got {str(type(mol_in))}"
logger.critical(error)
return None, error
try:
mol_out = self.charge_parent(mol_in)
except Exception as e:
error = f"charge_parent FAILED: {str(e).strip()}"
logger.critical(error)
return None, error
if self._canon_taut:
try:
res = self.taut_enumerator.Enumerate(mol_out, False)
except TypeError:
# we are still on the pre-2021 RDKit API
res = self.taut_enumerator.Enumerate(mol_out)
except Exception as e:
# something else went wrong
error = f"canon_taut FAILED: {str(e).strip()}"
logger.critical(error)
return None, error
n_tautomers = len(res)
if hasattr(res, "status"):
completed = res.status == rdMolStandardize.TautomerEnumeratorStatus.Completed
else:
# we are still on the pre-2021 RDKit API
completed = len(res) < 1000
if not completed:
n_tautomers = -n_tautomers
try:
mol_out = self.taut_enumerator.PickCanonical(res)
except AttributeError:
# we are still on the pre-2021 RDKit API
mol_out = max([(self.taut_enumerator.ScoreTautomer(m), m) for m in res])[1]
except Exception as e:
# something else went wrong
error = f"canon_taut FAILED: {str(e).strip()}"
logger.critical(error)
return None, error
mol_out.SetProp("_Name", name)
return mol_out, n_tautomers |