# -*- Mode: python; tab-width: 4; indent-tabs-mode:nil; coding:utf-8 -*-
# vim: tabstop=4 expandtab shiftwidth=4 softtabstop=4
#
# MDAnalysis --- https://www.mdanalysis.org
# Copyright (c) 2006-2017 The MDAnalysis Development Team and contributors
# (see the file AUTHORS for the full list of names)
#
# Released under the GNU Public Licence, v2 or any higher version
#
# Please cite your use of MDAnalysis in published work:
#
# R. J. Gowers, M. Linke, J. Barnoud, T. J. E. Reddy, M. N. Melo, S. L. Seyler,
# D. L. Dotson, J. Domanski, S. Buchoux, I. M. Kenney, and O. Beckstein.
# MDAnalysis: A Python package for the rapid analysis of molecular dynamics
# simulations. In S. Benthall and S. Rostrup editors, Proceedings of the 15th
# Python in Science Conference, pages 102-109, Austin, TX, 2016. SciPy.
# doi: 10.25080/majora-629e541a-00e
#
# N. Michaud-Agrawal, E. J. Denning, T. B. Woolf, and O. Beckstein.
# MDAnalysis: A Toolkit for the Analysis of Molecular Dynamics Simulations.
# J. Comput. Chem. 32 (2011), 2319--2327, doi:10.1002/jcc.21787
#
"""RDKit molecule I/O --- :mod:`MDAnalysis.converters.RDKit`
================================================================
Read coordinates data from an `RDKit <https://www.rdkit.org/docs/>`__ :class:`rdkit.Chem.rdchem.Mol` with
:class:`RDKitReader` into an MDAnalysis Universe. Convert it back to a
:class:`rdkit.Chem.rdchem.Mol` with :class:`RDKitConverter`.
Example
-------
To read an RDKit molecule and then convert the AtomGroup back to an RDKit
molecule::
>>> from rdkit import Chem
>>> import MDAnalysis as mda
>>> mol = Chem.MolFromMol2File("docking_poses.mol2", removeHs=False)
>>> u = mda.Universe(mol)
>>> u
<Universe with 42 atoms>
>>> u.trajectory
<RDKitReader with 10 frames of 42 atoms>
>>> u.atoms.convert_to("RDKIT")
<rdkit.Chem.rdchem.Mol object at 0x7fcebb958148>
.. warning::
The RDKit converter is currently *experimental* and may not work as
expected for all molecules. Currently the converter accurately
infers the structures of approximately 99% of the `ChEMBL27`_ dataset.
Work is currently ongoing on further improving this and updates to the
converter are expected in future releases of MDAnalysis.
Please see `Issue #3339`_ and the `RDKitConverter benchmark`_ for more
details.
Classes
-------
.. autoclass:: RDKitReader
:members:
.. autoclass:: RDKitConverter
:members:
.. autofunction:: _infer_bo_and_charges
.. autofunction:: _standardize_patterns
.. autofunction:: _rebuild_conjugated_bonds
.. Links
.. _`ChEMBL27`: https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_27/
.. _`Issue #3339`: https://github.com/MDAnalysis/mdanalysis/issues/3339
.. _`RDKitConverter benchmark`: https://github.com/MDAnalysis/RDKitConverter-benchmark
"""
import copy
import warnings
from functools import lru_cache
from io import StringIO
import numpy as np
from . import base
from ..coordinates import memory
from ..coordinates.PDB import PDBWriter
from ..core.topologyattrs import _TOPOLOGY_ATTRS
from ..exceptions import NoDataError
try:
from rdkit import Chem
from rdkit.Chem import AllChem
except ImportError:
pass
else:
RDBONDORDER = {
1: Chem.BondType.SINGLE,
1.5: Chem.BondType.AROMATIC,
"ar": Chem.BondType.AROMATIC,
2: Chem.BondType.DOUBLE,
3: Chem.BondType.TRIPLE,
}
# add string version of the key for each bond
RDBONDORDER.update({str(key): value for key, value in RDBONDORDER.items()})
RDATTRIBUTES = {
"altLocs": "AltLoc",
"chainIDs": "ChainId",
"icodes": "InsertionCode",
"names": "Name",
"occupancies": "Occupancy",
"resnames": "ResidueName",
"resids": "ResidueNumber",
"segindices": "SegmentNumber",
"tempfactors": "TempFactor",
}
PERIODIC_TABLE = Chem.GetPeriodicTable()
# charges that should be assigned to monatomic cations
# structure --> atomic number : formal charge
# anion charges are directly handled by the code using the typical valence
# of the atom
MONATOMIC_CATION_CHARGES = {
3: 1, 11: 1, 19: 1, 37: 1, 47: 1, 55: 1,
12: 2, 20: 2, 29: 2, 30: 2, 38: 2, 56: 2,
26: 2, # Fe could also be +3
13: 3,
}
# reactions uses by _standardize_patterns to fix challenging cases
# must have single reactant and product, and cannot add any atom
STANDARDIZATION_REACTIONS = [
"[C-;X2;H0:1]=[O:2]>>[C+0:1]=[O:2]", # Cterm
"[N-;X2;H1;$(N-[*^3]):1]>>[N+0:1]", # Nterm
"[#6-:1]-[#6:2]=[O:3]>>[#6+0:1]=[#6:2]-[O-:3]", # keto-enolate
"[C-;v3:1]-[#7+0;v3;H2:2]>>[#6+0:1]=[#7+:2]", # ARG
"[#6+0;H0:1]=[#6+0:2]-[#7;X3:3]-[#6-;X3:4]"
">>[#6:1]=[#6:2]-[#7+:3]=[#6+0:4]", # HIP
"[S;D4;!v6:1]-[*-:2]>>[S;v6:1]=[*+0:2]", # sulfone
"[#7+0;X3:1]-[*-:2]>>[#7+:1]=[*+0:2]", # charged-N
]
_deduce_PDB_atom_name = PDBWriter(StringIO())._deduce_PDB_atom_name
[docs]
class RDKitReader(memory.MemoryReader):
"""Coordinate reader for RDKit.
.. versionadded:: 2.0.0
"""
format = 'RDKIT'
# Structure.coordinates always in Angstrom
units = {'time': None, 'length': 'Angstrom'}
@staticmethod
def _format_hint(thing):
"""Can this reader read *thing*?"""
try:
from rdkit import Chem
except ImportError:
# if we can't import rdkit, it's probably not rdkit
return False
else:
return isinstance(thing, Chem.Mol)
def __init__(self, filename, **kwargs):
"""Read coordinates from an RDKit molecule.
Each conformer in the original RDKit molecule will be read as a frame
in the resulting universe.
Parameters
----------
filename : rdkit.Chem.rdchem.Mol
RDKit molecule
"""
n_atoms = filename.GetNumAtoms()
coordinates = np.array([
conf.GetPositions() for conf in filename.GetConformers()],
dtype=np.float32)
if coordinates.size == 0:
warnings.warn("No coordinates found in the RDKit molecule")
coordinates = np.empty((1, n_atoms, 3), dtype=np.float32)
coordinates[:] = np.nan
super(RDKitReader, self).__init__(coordinates, order='fac', **kwargs)
[docs]
class RDKitConverter(base.ConverterBase):
"""Convert MDAnalysis :class:`~MDAnalysis.core.groups.AtomGroup` or
:class:`~MDAnalysis.core.universe.Universe` to RDKit
:class:`~rdkit.Chem.rdchem.Mol`
MDanalysis attributes are stored in each RDKit
:class:`~rdkit.Chem.rdchem.Atom` of the resulting molecule in two different
ways:
* in an :class:`~rdkit.Chem.rdchem.AtomPDBResidueInfo` object available
through the :meth:`~rdkit.Chem.rdchem.Atom.GetMonomerInfo` method if it's
an attribute that is typically found in a PDB file,
* directly as an atom property available through the
:meth:`~rdkit.Chem.rdchem.Atom.GetProp` methods for the others.
Supported attributes:
+-----------------------+-------------------------------------------+
| MDAnalysis attribute | RDKit |
+=======================+===========================================+
| altLocs | atom.GetMonomerInfo().GetAltLoc() |
+-----------------------+-------------------------------------------+
| chainIDs | atom.GetMonomerInfo().GetChainId() |
+-----------------------+-------------------------------------------+
| icodes | atom.GetMonomerInfo().GetInsertionCode() |
+-----------------------+-------------------------------------------+
| names | atom.GetMonomerInfo().GetName() |
| | atom.GetProp("_MDAnalysis_name") |
+-----------------------+-------------------------------------------+
| occupancies | atom.GetMonomerInfo().GetOccupancy() |
+-----------------------+-------------------------------------------+
| resnames | atom.GetMonomerInfo().GetResidueName() |
+-----------------------+-------------------------------------------+
| resids | atom.GetMonomerInfo().GetResidueNumber() |
+-----------------------+-------------------------------------------+
| segindices | atom.GetMonomerInfo().GetSegmentNumber() |
+-----------------------+-------------------------------------------+
| tempfactors | atom.GetMonomerInfo().GetTempFactor() |
+-----------------------+-------------------------------------------+
| charges | atom.GetDoubleProp("_MDAnalysis_charge") |
+-----------------------+-------------------------------------------+
| indices | atom.GetIntProp("_MDAnalysis_index") |
+-----------------------+-------------------------------------------+
| segids | atom.GetProp("_MDAnalysis_segid") |
+-----------------------+-------------------------------------------+
| types | atom.GetProp("_MDAnalysis_type") |
+-----------------------+-------------------------------------------+
Example
-------
To access MDAnalysis properties::
>>> import MDAnalysis as mda
>>> from MDAnalysis.tests.datafiles import PDB_full
>>> u = mda.Universe(PDB_full)
>>> mol = u.select_atoms('resname DMS').convert_to('RDKIT')
>>> mol.GetAtomWithIdx(0).GetMonomerInfo().GetResidueName()
'DMS'
To create a molecule for each frame of a trajectory::
from MDAnalysisTests.datafiles import PSF, DCD
from rdkit.Chem.Descriptors3D import Asphericity
u = mda.Universe(PSF, DCD, to_guess=['elements'])
ag = u.select_atoms("resid 1-10")
for ts in u.trajectory:
mol = ag.convert_to("RDKIT")
x = Asphericity(mol)
Notes
-----
The converter requires the :class:`~MDAnalysis.core.topologyattrs.Elements`
attribute to be present in the topology, else it will fail.
It also requires the `bonds` attribute, although they will be automatically
guessed if not present.
Hydrogens should be explicit in the topology file. If this is not the case,
use the parameter ``NoImplicit=False`` when using the converter to allow
implicit hydrogens and disable inferring bond orders and charges.
Since one of the main use case of the converter is converting trajectories
and not just a topology, creating a new molecule from scratch for every
frame would be too slow so the converter uses a caching system. The cache
only stores the 2 most recent AtomGroups that were converted, and is
sensitive to the arguments that were passed to the converter. The number of
objects cached can be changed with the function
:func:`set_converter_cache_size`. However, ``ag.convert_to("RDKIT")``
followed by ``ag.convert_to("RDKIT", NoImplicit=False)`` will not use the
cache since the arguments given are different. You can pass a
``cache=False`` argument to the converter to bypass the caching system.
The ``_MDAnalysis_index`` property of the resulting molecule corresponds
to the index of the specific :class:`~MDAnalysis.core.groups.AtomGroup`
that was converted, which may not always match the ``index`` property.
To get a better understanding of how the converter works under the hood,
please refer to the following RDKit UGM presentation:
* `Video (4:55 to 8:05) <https://youtu.be/5b5wYmK4URU>`__
* `Slides <https://github.com/rdkit/UGM_2020/blob/master/Presentations/C%C3%A9dricBouysset_From_RDKit_to_the_Universe.pdf>`__
There are some molecules containing specific patterns that the converter
cannot currently tackle correctly. See
`Issue #3339 <https://github.com/MDAnalysis/mdanalysis/issues/3339>`__ for
more info.
.. versionadded:: 2.0.0
.. versionchanged:: 2.2.0
Improved the accuracy of the converter. Atoms in the resulting molecule
now follow the same order as in the AtomGroup. The output of
``atom.GetMonomerInfo().GetName()`` now follows the guidelines for PDB
files while the original name is still available through
``atom.GetProp("_MDAnalysis_name")``
"""
lib = 'RDKIT'
units = {'time': None, 'length': 'Angstrom'}
[docs]
def convert(self, obj, cache=True, NoImplicit=True, max_iter=200,
force=False):
"""Write selection at current trajectory frame to
:class:`~rdkit.Chem.rdchem.Mol`.
Parameters
-----------
obj : :class:`~MDAnalysis.core.groups.AtomGroup` or :class:`~MDAnalysis.core.universe.Universe`
cache : bool
Use a cached copy of the molecule's topology when available. To be
used, the cached molecule and the new one have to be made from the
same AtomGroup selection and with the same arguments passed
to the converter
NoImplicit : bool
Prevent adding hydrogens to the molecule
max_iter : int
Maximum number of iterations to standardize conjugated systems.
See :func:`_rebuild_conjugated_bonds`
force : bool
Force the conversion when no hydrogens were detected but
``NoImplicit=True``. Useful for inorganic molecules mostly.
"""
try:
from rdkit import Chem
except ImportError:
raise ImportError("RDKit is required for the RDKitConverter but "
"it's not installed. Try installing it with \n"
"conda install -c conda-forge rdkit")
try:
# make sure to use atoms (Issue 46)
ag = obj.atoms
except AttributeError:
raise TypeError("No `atoms` attribute in object of type {}, "
"please use a valid AtomGroup or Universe".format(
type(obj))) from None
# parameters passed to atomgroup_to_mol
kwargs = dict(NoImplicit=NoImplicit, max_iter=max_iter, force=force)
if cache:
mol = atomgroup_to_mol(ag, **kwargs)
mol = copy.deepcopy(mol)
else:
mol = atomgroup_to_mol.__wrapped__(ag, **kwargs)
# add a conformer for the current Timestep
if hasattr(ag, "positions"):
if np.isnan(ag.positions).any():
warnings.warn("NaN detected in coordinates, the output "
"molecule will not have 3D coordinates assigned")
else:
# assign coordinates
conf = Chem.Conformer(mol.GetNumAtoms())
for atom in mol.GetAtoms():
idx = atom.GetIdx()
xyz = ag.positions[idx].astype(float)
conf.SetAtomPosition(idx, xyz)
mol.AddConformer(conf)
# assign R/S to atoms and Z/E to bonds
Chem.AssignStereochemistryFrom3D(mol)
Chem.SetDoubleBondNeighborDirections(mol)
return mol
@lru_cache(maxsize=2)
def atomgroup_to_mol(ag, NoImplicit=True, max_iter=200, force=False):
"""Converts an AtomGroup to an RDKit molecule without coordinates.
Parameters
-----------
ag : MDAnalysis.core.groups.AtomGroup
The AtomGroup to convert
NoImplicit : bool
Prevent adding hydrogens to the molecule and allow bond orders and
formal charges to be guessed from the valence of each atom.
max_iter : int
Maximum number of iterations to standardize conjugated systems.
See :func:`_rebuild_conjugated_bonds`
force : bool
Force the conversion when no hydrogens were detected but
``NoImplicit=True``. Mostly useful for inorganic molecules.
"""
try:
elements = ag.elements
except NoDataError:
raise AttributeError(
"The `elements` attribute is required for the RDKitConverter "
"but is not present in this AtomGroup. Please refer to the "
"documentation to guess elements from other attributes or "
"type `help(MDAnalysis.topology.guessers)`") from None
if "H" not in ag.elements:
if force:
warnings.warn(
"No hydrogen atom found in the topology. "
"Forcing to continue the conversion."
)
elif NoImplicit:
raise AttributeError(
"No hydrogen atom could be found in the topology, but the "
"converter requires all hydrogens to be explicit. You can use "
"the parameter ``NoImplicit=False`` when using the converter "
"to allow implicit hydrogens and disable inferring bond "
"orders and charges. You can also use ``force=True`` to "
"ignore this error.")
# attributes accepted in PDBResidueInfo object
pdb_attrs = {}
for attr in RDATTRIBUTES.keys():
if hasattr(ag, attr):
pdb_attrs[attr] = getattr(ag, attr)
resnames = pdb_attrs.get("resnames", None)
if resnames is None:
def get_resname(idx):
return ""
else:
def get_resname(idx):
return resnames[idx]
other_attrs = {}
for attr in ["charges", "segids", "types", "names"]:
if hasattr(ag, attr):
other_attrs[attr] = getattr(ag, attr)
mol = Chem.RWMol()
# map index in universe to index in mol
atom_mapper = {}
for i, (atom, element) in enumerate(zip(ag, elements)):
# create atom
rdatom = Chem.Atom(element.capitalize())
# enable/disable adding implicit H to the molecule
rdatom.SetNoImplicit(NoImplicit)
# add PDB-like properties
mi = Chem.AtomPDBResidueInfo()
for attr, values in pdb_attrs.items():
_add_mda_attr_to_rdkit(attr, values[i], mi, get_resname(i))
rdatom.SetMonomerInfo(mi)
# other properties
for attr in other_attrs.keys():
value = other_attrs[attr][i]
attr = "_MDAnalysis_%s" % _TOPOLOGY_ATTRS[attr].singular
_set_atom_property(rdatom, attr, value)
_set_atom_property(rdatom, "_MDAnalysis_index", i)
# add atom
index = mol.AddAtom(rdatom)
atom_mapper[atom.ix] = index
try:
ag.bonds
except NoDataError:
warnings.warn(
"No `bonds` attribute in this AtomGroup. Guessing bonds based "
"on atoms coordinates")
ag.guess_bonds()
for bond in ag.bonds:
try:
bond_indices = [atom_mapper[i] for i in bond.indices]
except KeyError:
continue
bond_type = RDBONDORDER.get(bond.order, Chem.BondType.SINGLE)
mol.AddBond(*bond_indices, bond_type)
mol.UpdatePropertyCache(strict=False)
if NoImplicit:
# infer bond orders and formal charges from the connectivity
_infer_bo_and_charges(mol)
mol = _standardize_patterns(mol, max_iter)
# reorder atoms to match MDAnalysis, since the reactions from
# _standardize_patterns will mess up the original order
order = np.argsort([atom.GetIntProp("_MDAnalysis_index")
for atom in mol.GetAtoms()])
mol = Chem.RenumberAtoms(mol, order.astype(int).tolist())
# sanitize if possible
err = Chem.SanitizeMol(mol, catchErrors=True)
if err:
warnings.warn("Could not sanitize molecule: "
f"failed during step {err!r}")
return mol
def set_converter_cache_size(maxsize):
"""Set the maximum cache size of the RDKit converter
Parameters
----------
maxsize : int or None
If int, the cache will only keep the ``maxsize`` most recent
conversions in memory. Using ``maxsize=None`` will remove all limits
to the cache size, i.e. everything is cached.
"""
global atomgroup_to_mol # pylint: disable=global-statement
atomgroup_to_mol = lru_cache(maxsize=maxsize)(atomgroup_to_mol.__wrapped__)
def _add_mda_attr_to_rdkit(attr, value, mi, resname=""):
"""Converts an MDAnalysis atom attribute into the RDKit equivalent and
stores it into an RDKit :class:`~rdkit.Chem.rdchem.AtomPDBResidueInfo`.
Parameters
----------
attr : str
Name of the atom attribute in MDAnalysis in the singular form
value : object, np.int or np.float
Attribute value as found in the AtomGroup
mi : rdkit.Chem.rdchem.AtomPDBResidueInfo
MonomerInfo object that will store the relevant atom attributes
resname : str
Residue name of the atom, if available
"""
if isinstance(value, np.generic):
# convert numpy types to python standard types
value = value.item()
if attr == "names":
# RDKit needs the name to be properly formatted for a PDB file
value = _deduce_PDB_atom_name(value, resname)
# set attribute value in RDKit MonomerInfo
rdattr = RDATTRIBUTES[attr]
getattr(mi, "Set%s" % rdattr)(value)
def _set_str_prop(atom, attr, value):
atom.SetProp(attr, value)
def _set_float_prop(atom, attr, value):
atom.SetDoubleProp(attr, value)
def _set_np_float_prop(atom, attr, value):
atom.SetDoubleProp(attr, float(value))
def _set_int_prop(atom, attr, value):
atom.SetIntProp(attr, value)
def _set_np_int_prop(atom, attr, value):
atom.SetIntProp(attr, int(value))
def _ignore_prop(atom, attr, value):
pass
_atom_property_dispatcher = {
str: _set_str_prop,
float: _set_float_prop,
np.float32: _set_np_float_prop,
np.float64: _set_np_float_prop,
int: _set_int_prop,
np.int8: _set_np_int_prop,
np.int16: _set_np_int_prop,
np.int32: _set_np_int_prop,
np.int64: _set_np_int_prop,
np.uint8: _set_np_int_prop,
np.uint16: _set_np_int_prop,
np.uint32: _set_np_int_prop,
np.uint64: _set_np_int_prop,
}
def _set_atom_property(atom, attr, value):
"""Saves any attribute and value into an RDKit atom property"""
_atom_property_dispatcher.get(type(value), _ignore_prop)(atom, attr, value)
def _atom_sorter(atom):
"""Sorts atoms in the molecule in a way that makes it easy for the bond
order and charge infering code to get the correct state on the first
try. Currently sorts by number of unpaired electrons, then by number of
heavy atom neighbors (i.e. atoms at the edge first)."""
num_heavy_neighbors = len([
neighbor for neighbor in atom.GetNeighbors()
if neighbor.GetAtomicNum() > 1]
)
return (-_get_nb_unpaired_electrons(atom)[0], num_heavy_neighbors)
[docs]
def _infer_bo_and_charges(mol):
"""Infer bond orders and formal charges from a molecule.
Since most MD topology files don't explicitly retain information on bond
orders or charges, it has to be guessed from the topology. This is done by
looping over each atom and comparing its expected valence to the current
valence to get the Number of Unpaired Electrons (NUE).
If an atom has a negative NUE, it needs a positive formal charge (-NUE).
If two neighbouring atoms have UEs, the bond between them most
likely has to be increased by the value of the smallest NUE.
If after this process, an atom still has UEs, it needs a negative formal
charge of -NUE.
Parameters
----------
mol : rdkit.Chem.rdchem.RWMol
The molecule is modified inplace and must have all hydrogens added
Notes
-----
This algorithm is order dependant. For example, for a carboxylate group
R-C(-O)-O the first oxygen read will receive a double bond and the other
one will be charged. It will also affect more complex conjugated systems.
"""
# heavy atoms sorted by number of heavy atom neighbors (lower first) then
# NUE (higher first)
atoms = sorted([atom for atom in mol.GetAtoms()
if atom.GetAtomicNum() > 1],
key=_atom_sorter)
for atom in atoms:
# monatomic ions
if atom.GetDegree() == 0:
atom.SetFormalCharge(MONATOMIC_CATION_CHARGES.get(
atom.GetAtomicNum(),
-_get_nb_unpaired_electrons(atom)[0]))
mol.UpdatePropertyCache(strict=False)
continue
# get NUE for each possible valence
nue = _get_nb_unpaired_electrons(atom)
# if there's only one possible valence state and the corresponding
# NUE is negative, it means we can only add a positive charge to
# the atom
if (len(nue) == 1) and (nue[0] < 0):
atom.SetFormalCharge(-nue[0])
mol.UpdatePropertyCache(strict=False)
# go to next atom if above case or atom has no unpaired electron
if (len(nue) == 1) and (nue[0] <= 0):
continue
else:
neighbors = sorted(atom.GetNeighbors(), reverse=True,
key=lambda a: _get_nb_unpaired_electrons(a)[0])
# check if one of the neighbors has a common NUE
for na in neighbors:
# get NUE for the neighbor
na_nue = _get_nb_unpaired_electrons(na)
# smallest common NUE
common_nue = min(
min([i for i in nue if i >= 0], default=0),
min([i for i in na_nue if i >= 0], default=0)
)
# a common NUE of 0 means we don't need to do anything
if common_nue != 0:
# increase bond order
bond = mol.GetBondBetweenAtoms(
atom.GetIdx(), na.GetIdx())
order = common_nue + 1
bond.SetBondType(RDBONDORDER[order])
mol.UpdatePropertyCache(strict=False)
# go to next atom if one of the valences is complete
nue = _get_nb_unpaired_electrons(atom)
if any([n == 0 for n in nue]):
break
# if atom valence is still not filled
nue = _get_nb_unpaired_electrons(atom)
if not any([n == 0 for n in nue]):
# transform nue to charge
atom.SetFormalCharge(-nue[0])
atom.SetNumRadicalElectrons(0)
mol.UpdatePropertyCache(strict=False)
def _get_nb_unpaired_electrons(atom):
"""Calculate the number of unpaired electrons (NUE) of an atom
Parameters
----------
atom: rdkit.Chem.rdchem.Atom
The atom for which the NUE will be computed
Returns
-------
nue : list
The NUE for each possible valence of the atom
"""
expected_vs = PERIODIC_TABLE.GetValenceList(atom.GetAtomicNum())
current_v = atom.GetTotalValence() - atom.GetFormalCharge()
return [v - current_v for v in expected_vs]
[docs]
def _standardize_patterns(mol, max_iter=200):
"""Standardizes functional groups
Uses :func:`_rebuild_conjugated_bonds` to standardize conjugated systems,
and SMARTS reactions for other functional groups.
Due to the way reactions work, we first have to split the molecule by
fragments. Then, for each fragment, we apply the standardization reactions.
Finally, the fragments are recombined.
Parameters
----------
mol : rdkit.Chem.rdchem.RWMol
The molecule to standardize
max_iter : int
Maximum number of iterations to standardize conjugated systems
Returns
-------
mol : rdkit.Chem.rdchem.Mol
The standardized molecule
Notes
-----
The following functional groups are transformed in this order:
+---------------+------------------------------------------------------------------------------+
| Name | Reaction |
+===============+==============================================================================+
| conjugated | ``[*-:1]-[*:2]=[*:3]-[*-:4]>>[*+0:1]=[*:2]-[*:3]=[*+0:4]`` |
+---------------+------------------------------------------------------------------------------+
| conjugated N+ | ``[N;X3;v3:1]-[*:2]=[*:3]-[*-:4]>>[N+:1]=[*:2]-[*:3]=[*+0:4]`` |
+---------------+------------------------------------------------------------------------------+
| conjugated O- | ``[O:1]=[#6+0,#7+:2]-[*:3]=[*:4]-[*-:5]>>[O-:1]-[*:2]=[*:3]-[*:4]=[*+0:5]`` |
+---------------+------------------------------------------------------------------------------+
| conjug. S=O | ``[O-:1]-[S;D4;v4:2]-[*:3]=[*:4]-[*-:5]>>[O+0:1]=[*:2]=[*:3]-[*:4]=[*+0:5]`` |
+---------------+------------------------------------------------------------------------------+
| Cterm | ``[C-;X2;H0:1]=[O:2]>>[C+0:1]=[O:2]`` |
+---------------+------------------------------------------------------------------------------+
| Nterm | ``[N-;X2;H1;$(N-[*^3]):1]>>[N+0:1]`` |
+---------------+------------------------------------------------------------------------------+
| keto-enolate | ``[#6-:1]-[#6:2]=[O:3]>>[#6+0:1]=[#6:2]-[O-:3]`` |
+---------------+------------------------------------------------------------------------------+
| arginine | ``[C-;v3:1]-[#7+0;v3;H2:2]>>[#6+0:1]=[#7+:2]`` |
+---------------+------------------------------------------------------------------------------+
| histidine | ``[#6+0;H0:1]=[#6+0:2]-[#7;X3:3]-[#6-;X3:4]>>[#6:1]=[#6:2]-[#7+:3]=[#6+0:4]``|
+---------------+------------------------------------------------------------------------------+
| sulfone | ``[S;D4;!v6:1]-[*-:2]>>[S;v6:1]=[*+0:2]`` |
+---------------+------------------------------------------------------------------------------+
| charged N | ``[#7+0;X3:1]-[*-:2]>>[#7+:1]=[*+0:2]`` |
+---------------+------------------------------------------------------------------------------+
"""
# standardize conjugated systems
_rebuild_conjugated_bonds(mol, max_iter)
# list of sanitized reactions
reactions = []
for rxn in STANDARDIZATION_REACTIONS:
reaction = AllChem.ReactionFromSmarts(rxn)
reactions.append(reaction)
# fragment mol (reactions must have single reactant and product)
fragments = list(Chem.GetMolFrags(mol, asMols=True))
for reactant in fragments:
_apply_reactions(reactions, reactant)
# recombine fragments
newmol = fragments.pop(0)
for fragment in fragments:
newmol = Chem.CombineMols(newmol, fragment)
return newmol
def _apply_reactions(reactions, reactant):
"""Applies a series of unimolecular reactions to a molecule. The reactions
must not add any atom to the product. The molecule is modified inplace.
Parameters
----------
reactions : List[rdkit.Chem.rdChemReactions.ChemicalReaction]
Reactions from SMARTS. Each reaction is applied until no more
transformations can be made.
reactant : rdkit.Chem.rdchem.Mol
The molecule to transform inplace
"""
reactant.UpdatePropertyCache(strict=False)
Chem.Kekulize(reactant)
for reaction in reactions:
while reaction.RunReactantInPlace(reactant):
reactant.UpdatePropertyCache(strict=False)
reactant.UpdatePropertyCache(strict=False)
Chem.Kekulize(reactant)
[docs]
def _rebuild_conjugated_bonds(mol, max_iter=200):
"""Rebuild conjugated bonds without negatively charged atoms at the
beginning and end of the conjugated system
Depending on the order in which atoms are read during the conversion, the
:func:`_infer_bo_and_charges` function might write conjugated systems with
a double bond less and both edges of the system as anions instead of the
usual alternating single and double bonds. This function corrects this
behaviour by using an iterative procedure.
The problematic molecules always follow the same pattern:
``anion[-*=*]n-anion`` instead of ``*=[*-*=]n*``, where ``n`` is the number
of successive single and double bonds. The goal of the iterative procedure
is to make ``n`` as small as possible by consecutively transforming
``anion-*=*`` into ``*=*-anion`` until it reaches the smallest pattern with
``n=1``. This last pattern is then transformed from ``anion-*=*-anion`` to
``*=*-*=*``.
Since ``anion-*=*`` is the same as ``*=*-anion`` in terms of SMARTS, we can
control that we don't transform the same triplet of atoms back and forth by
adding their indices to a list.
This function also handles conjugated systems with triple bonds.
The molecule needs to be kekulized first to also cover systems
with aromatic rings.
Parameters
----------
mol : rdkit.Chem.rdchem.RWMol
The molecule to transform, modified inplace
max_iter : int
Maximum number of iterations performed by the function
Notes
-----
The molecule is modified inplace
"""
mol.UpdatePropertyCache(strict=False)
Chem.Kekulize(mol)
# pattern used to find problematic conjugated bonds
# there's usually an even number of matches for this
pattern = Chem.MolFromSmarts("[*-{1-2}]-,=[*+0]=,#[*+0]")
# pattern used to finish fixing a series of conjugated bonds
base_end_pattern = Chem.MolFromSmarts(
"[*-{1-2}]-,=[*+0]=,#[*+0]-,=[*-{1-2}]")
# used when there's an odd number of matches for `pattern`
odd_end_pattern = Chem.MolFromSmarts(
"[*-]-[*+0]=[*+0]-[*-,$([#7;X3;v3]),$([#6+0,#7+1]=O),"
"$([S;D4;v4]-[O-])]")
# number of unique matches with the pattern
n_matches = len(set([match[0]
for match in mol.GetSubstructMatches(pattern)]))
# nothing to standardize
if n_matches == 0:
return
# single match (unusual)
elif n_matches == 1:
# as a last resort, the only way to standardize is to find a nitrogen
# that can accept a double bond and a positive charge
# or a carbonyl that will become an enolate
end_pattern = odd_end_pattern
# at least 2 matches
else:
# give priority to base end pattern and then deal with the odd one if
# necessary
end_pattern = base_end_pattern
backtrack = []
backtrack_cycles = 0
for _ in range(max_iter):
# check for ending pattern
end_match = mol.GetSubstructMatch(end_pattern)
if end_match:
# index of each atom
anion1, a1, a2, anion2 = end_match
term_atom = mol.GetAtomWithIdx(anion2)
# edge-case 1: C-[O-] or [N+]-[O-]
# [*-]-*=*-[C,N+]=O --> *=*-*=[C,N+]-[O-]
# transform the =O to -[O-]
if (
term_atom.GetAtomicNum() == 6
and term_atom.GetFormalCharge() == 0
) or (
term_atom.GetAtomicNum() == 7
and term_atom.GetFormalCharge() == 1
):
for neighbor in term_atom.GetNeighbors():
bond = mol.GetBondBetweenAtoms(anion2, neighbor.GetIdx())
if (neighbor.GetAtomicNum() == 8 and
bond.GetBondTypeAsDouble() == 2):
bond.SetBondType(Chem.BondType.SINGLE)
neighbor.SetFormalCharge(-1)
break
# edge-case 2: S=O
# [*-]-*=*-[Sv4]-[O-] --> *=*-*=[Sv6]=O
# transform -[O-] to =O
elif (term_atom.GetAtomicNum() == 16 and
term_atom.GetFormalCharge() == 0):
for neighbor in term_atom.GetNeighbors():
bond = mol.GetBondBetweenAtoms(anion2, neighbor.GetIdx())
if (neighbor.GetAtomicNum() == 8 and
neighbor.GetFormalCharge() == -1 and
bond.GetBondTypeAsDouble() == 1):
bond.SetBondType(Chem.BondType.DOUBLE)
neighbor.SetFormalCharge(0)
break
# not an edge case:
# increment the charge
else:
term_atom.SetFormalCharge(term_atom.GetFormalCharge() + 1)
# common to all cases:
# [*-]-*=*-[R] --> *=*-*=[R]
# increment the charge and switch single and double bonds
a = mol.GetAtomWithIdx(anion1)
a.SetFormalCharge(a.GetFormalCharge() + 1)
b = mol.GetBondBetweenAtoms(anion1, a1)
b.SetBondType(RDBONDORDER[b.GetBondTypeAsDouble() + 1])
b = mol.GetBondBetweenAtoms(a1, a2)
b.SetBondType(RDBONDORDER[b.GetBondTypeAsDouble() - 1])
b = mol.GetBondBetweenAtoms(a2, anion2)
b.SetBondType(RDBONDORDER[b.GetBondTypeAsDouble() + 1])
mol.UpdatePropertyCache(strict=False)
continue
# switch the position of the charge and the double bond
matches = mol.GetSubstructMatches(pattern)
if matches:
# check if we haven't already transformed this triplet
for match in matches:
# store order-independent atom indices
g = set(match)
# already transformed --> try the next one
if g in backtrack:
continue
# add to backtracking and start the switch
else:
anion, a1, a2 = match
backtrack.append(g)
break
# already performed all changes
else:
if backtrack_cycles == 1:
# might be stuck because there were 2 "odd" end patterns
# misqualified as a single base one
end_pattern = odd_end_pattern
elif backtrack_cycles > 1:
# likely stuck changing the same bonds over and over so
# let's stop here
mol.UpdatePropertyCache(strict=False)
return
match = matches[0]
anion, a1, a2 = match
backtrack = [set(match)]
backtrack_cycles += 1
# switch charges
a = mol.GetAtomWithIdx(anion)
a.SetFormalCharge(a.GetFormalCharge() + 1)
a = mol.GetAtomWithIdx(a2)
a.SetFormalCharge(a.GetFormalCharge() - 1)
# switch bond orders
b = mol.GetBondBetweenAtoms(anion, a1)
b.SetBondType(RDBONDORDER[b.GetBondTypeAsDouble() + 1])
b = mol.GetBondBetweenAtoms(a1, a2)
b.SetBondType(RDBONDORDER[b.GetBondTypeAsDouble() - 1])
mol.UpdatePropertyCache(strict=False)
# update number of matches for the end pattern
n_matches = len(set([match[0] for match in matches]))
if n_matches == 1:
end_pattern = odd_end_pattern
# start new iteration
continue
# no more changes to apply
mol.UpdatePropertyCache(strict=False)
return
# reached max_iter
warnings.warn("The standardization could not be completed within a "
"reasonable number of iterations")