Re: [Rdkit-discuss] Question on chirality

Jan Holst Jensen Fri, 13 Sep 2019 02:51:49 -0700

Hi Navid,

I am not familiar with the paper you mention, but I believe that the problem is caused by non-isomeric input SMILES.

Below is an Alanine read in from molfile, with coordinates. It has a chiral center with "S" configuration. When you output it as non-isomeric SMILES and read it back in, the chiral information is lost because the molecule no longer has a conformation:


    >>> mol = Chem.MolFromMolBlock("""
   ...   BIOCHEMF09131911262D
   ...
   ...   7  6  0  0  1  0  0  0  0  0999 V2000
   ...     0.0000    0.0000    0.0000 N   0  0  0  0  0  0  0 0  0  0  0  0
   ...     0.7145    0.4125    0.0000 C   0  0  0  0  0  0  0 0  0  0  0  0
   ...     1.4290    0.0000    0.0000 C   0  0  0  0  0  0  0 0  0  0  0  0
   ...     1.4209   -0.8208    0.0000 O   0  0  0  0  0  0  0 0  0  0  0  0
   ...     0.7084    1.2417    0.0000 C   0  0  0  0  0  0  0 0  0  0  0  0
   ...    -1.0000    0.0000    0.0000 H   0  0  0  0  0  0  0 0  0  0  0  0
   ...     2.4290    0.0000    0.0000 O   0  0  0  0  0  0  0 0  0  0  0  0
   ...   2  3  1  0  0  0  0
   ...   1  2  1  0  0  0  0
   ...   3  4  2  0  0  0  0
   ...   2  5  1  1  0  0  0
   ...   1  6  1  0  0  0  0
   ...   3  7  1  0  0  0  0
   ... M  END
   ... """)
    >>> Chem.AssignAtomChiralTagsFromStructure(mol)
    >>> Chem.FindMolChiralCenters(mol)
   [(1, 'S')]
    >>> Chem.MolToSmiles(mol)
   'CC(N)C(=O)O'
    >>> mol = Chem.MolFromSmiles("CC(N)C(=O)O")
    >>> Chem.AssignAtomChiralTagsFromStructure(mol)
    >>> Chem.FindMolChiralCenters(mol)
   []
    >>>

You can generate a conformation that produces chiral information by 3D embedding the molecule.


    >>> from rdkit.Chem import AllChem
    >>> AllChem.EmbedMolecule(mol)
   0
    >>> Chem.AssignAtomChiralTagsFromStructure(mol)
    >>> Chem.FindMolChiralCenters(mol)
   [(1, 'S')]
    >>>

Another way would be if you can get isomeric SMILES as input. Then the chiral information is right there.


    >>> Chem.MolToSmiles(mol, isomericSmiles = True)
   'C[C*@*H](N)C(=O)O'
    >>> mol = Chem.MolFromSmiles("C[C@H](N)C(=O)O")
    >>> Chem.FindMolChiralCenters(mol)
   [(1, 'S')]
    >>>


Cheers
-- Jan Holst Jensen


On 2019-09-12 04:44, Navid Shervani-Tabar wrote:

Hello,

In the paper: "Graph Networks as a Universal Machine Learning
Framework for Molecules and Crystals", authors introduce chirality as an atom feature input to analyze QM9 dataset. I was trying to recreate this atom feature as following
> Chirality: (categorical) R, S, or not a Chiral center (one-hot encoded).

The code I used is:

    from chainer_chemistry import datasets
from chainer_chemistry.dataset.preprocessors.ggnn_preprocessor import GGNNPreprocessor
    from rdkit import Chem
    import numpy as np
dataset, dataset_smiles = datasets.get_qm9(GGNNPreprocessor(), return_smiles=True)
    for i in range(len(dataset_smiles)):
        mol = Chem.MolFromSmiles(dataset_smiles[i])
        Chem.AssignAtomChiralTagsFromStructure(mol)
        chiral_cc = Chem.FindMolChiralCenters(mol)

        if not len(chiral_cc) == 0:
            print(chiral_cc)
The output shows no Chiral centers for this dataset. When I use `includeUnassigned=True`, code gives a list of tuples, but instead of "R/S", I get "?". I was wondering if there is a mistake in my implementation. If this is expected, any thoughts on how chirality was assigned in the above paper? Thanks.
Sincerely,
Navid

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