search

OpenFreeEnergy / kartograf

This package contains tools for setting up hybrid-topology FE calculations
https://kartograf.readthedocs.io/
MIT License
25 stars 3 forks source link

fused ring atom mapping/scoring for single/hybrid topology methods #44

Closed JenkeScheen closed 1 week ago

JenkeScheen commented 6 months ago

we've run into a few problematic mappings with the kartograf mapper for fused ring systems. kartograf maps the following example (red are atoms mapped to remove): image

But with single/hybrid topology methods this won't work. Instead, we would want a mapping like this: image which is of course not very efficient but with enough sampling is much more likely to give an accurate DDG estimate. If you want to reproduce our particular transformation you can use SMILES c1ccc(cc1)COC(=O)Nc2cc(cc(c2)Cl)C(=O)Nc3ccc4c(c3)CC[C@@H]4N and c1ccc(cc1)COC(=O)Nc2cc(cc(c2)Cl)C(=O)Nc3cccc(c3)[C@H]4CCNC4.

There are some implementations on allow ring breaking options for popular mappers, see here and here for some examples. Would it be in scope for kartograf to have this option too? Currently we need to revert back to perses mappers/scorers for this kind of transformation.

IAlibay commented 6 months ago

@JenkeScheen can you confirm what version of Kartograf you are using?

JenkeScheen commented 6 months ago

I've got kartograf 1.0.0 pyhd8ed1ab_3 conda-forge

IAlibay commented 6 months ago

Cheers @JenkeScheen, thanks for the report. We'll have a quick stab at this a bit later today / over the next few days - there are filters in place for preventing ring breaking (and one for not doing ring hybridization changes), will need to check why it's not working.

David-Araripe commented 4 months ago

Hi @JenkeScheen I happened to work on something similar and I did some processing on kartograf's output to obtain the following:

This was for a work that is yet unpublished but if you're still working on this let me know, happy to share some code