Re: [Rdkit-discuss] rejoining pairs of fragments after fragmenting a molecule

[Francois B. <ml...@li...>]

On 03/04/2021 00:03, Andrew Dalke wrote:
> Hi Ling,
> 
>> On Apr 2, 2021, at 16:23, Ling Chan <lin...@gm...> wrote:
>> 
>> Thank you Francois, I took a look at your code and borrowed parts of 
>> it to rejoin two molecules. It seems like my problem is solved. I 
>> eventually arrived at something like example 4 in
>> https://www.programcreek.com/python/example/123334/rdkit.Chem.CombineMols
>> (which I discovered a bit late).
>> 
>> Still, I am not sure if the code is safe. In particular, I wonder if 
>> the following conditions are always valid.
>> 	• Chem.CombineMols simply concatenates the atomic indices from the 
>> input molecules.
>> 	• The Chem.EditableMol constructor preserves atom ordering from the 
>> input.
>> 	• RemoveAtom in EditableMol results in all indices above the deleted 
>> to decrease by one, i.e. atom ordering is preserved.
> 
> I've found that it's very hard to work with molecular graphs and
> preserve stereochemistry.
> 
> Consider F/C=C/Cl breaking on the first bond, and the code I pointed 
> you to.
> 
> FragmentOnBonds() using '9' as the labels gives:  [9*]/C=C/Cl.[9*]F
> 
> My "smiles_weld" code converts that to: CC\%99=C/Cl.F%99 which can be
> re-canonicalized to the original: F/C=C/Cl .
> 
> Or, with F[C@H](Cl)Br again, breaking on the first bond.
> 
> FragmentOnBonds() gives [9*]F.[9*][C@H](Cl)Br
> 
> smiles_weld converts that to F%99.[C@@H]%99(Cl)Br which is
> re-canonicalized as  F[C@H](Cl)Br
> 
> Handling this correctly in the molecule API requires paying careful
> attention to the bond direction, and bond attachment order around the
> atom, which changes with RemoveAtom() calls. I didn't see
> stereochemistry support in Francois's "bind_molecules()" nor in the
> connect_mols() at

After discussing with an organic chemist, we decided that fragmenting 
(on the computer) molecules
on bonds which are involved in stereochemistry (stereo bond or linked to 
a stereo center)
is not desirable.
I.e. if the molecules being fragmented have stereochemistry assigned, we 
don't touch around it.

> https://github.com/molecularsets/moses/blob/master/moses/baselines/combinatorial.py
> (one of the examples from the programcreek.com link you gave).
> 
> If you don't need to support or preserve stereochemistry, then of
> course there's no problem.
> 
> Cheers,
> 
> 				Andrew
> 				da...@da...
> 
> 
> 
> 
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss