Interactions between cocrystallized cofactor and ligand

[michabirklbauer]

Greetings!

I am currently working with a lot of PDB structures that feature a cofactor cocrystallized in addtion to the ligand. I have been successfully extracting interactions between the cofactor and the protein and between the ligand and the protein with PLIP. However I would also like to have the interactions between the cofactor and the ligand - if there are any. So my question is, if it is possible to also get those interactions with PLIP?

As a sidenote, I have been working with PLIP in python and I think there is actually a line in PLIP that excludes ligand-ligand interactions (if I understood the code correctly): -> here

# Get all interacting residues, excluding ligand and water molecules
self.interacting_res = list(set([''.join([str(i.resnr), str(i.reschain)]) for i in self.all_itypes
                                          if i.restype not in ['LIG', 'HOH']]))

Would "LIG" be something that I would not want to exclude then or is it not all related to my problem?

Thanks for the help in advance and best regards!

[fkaiserbio]

Hi there!

Currently, this is not officially supported by PLIP. We already discussed this and came to the conclusion that a proper parameterization would be needed to obtain valid results. PLIP was extensively parameterized and tested only for the ligand / protein case, i.e. to reproduce literature-reported interactions.

However, changing this single line could indeed force PLIP to treat the cofactor as part of the binding site. This feature is not currently on the development plan and thus we welcome any contributions in that direction.

I hope that helped!

Best regards