RBFE for covalently bound ligands

[nffaruk]

This is for comparing covalent inhibitors - some papers seem to suggest that you can just use rbfe between the covalent states of the ligands instead of modeling the whole cycle of bond forming/breaking (e.g. https://doi.org/10.1021/acs.jcim.1c00515). I wonder if the implementation of this would overlap with the work done for protein mutations #1500 i.e. could the bound ligands be considered special residues. Any thoughts @ijpulidos

[IAlibay]

It is our aim to eventually allow individuals to do mutation RBFEs with arbitrarily modified residues.

However the path to enabling this requires the completion of a few ongoing/hopefully upcoming tasks;

• Being able to parameterize arbitrarily modified systems
• Being able to load such systems, including bond orders, into gufe/OpenFE
• Merging updates from FEFlow into core openfe protocols
• Maybe others I've not had time to think about yet.

We hope that some of these tasks may be prioritised in our next roadmap.

That being said, thinking about the science only, it is my understanding from discussions with our TAC that whether or not one should mutate post or pre covalent binding is still unresolved.

[nffaruk]

Thanks Irfan for the overview of what needs to be done