Cofactor in receptor

[ven828]

Hi, I have a target protein that contains a cofactor (small molecule) in the binding site and the workflow fails at the energy optimisation step (residue template missing error).

Any suggestions?

[bieniekmateusz]

Hey, openff now supports it so we should be able to add that. Would you be able to upload a system we can use for testing? Thanks

[bieniekmateusz]

Hi again. We currently use the SystemGenerator from the openmmforcefields package:
https://github.com/cole-group/FEgrow/blob/418190b1a73a3a927d5ae27a467206136d07b3c5/fegrow/receptor.py#L144C33-L149
To which we pass only one molecule. Co-factors should be passed here as well with molecules.

These are expected to be OFF Molecules, which can be built from Smiles or anything really.
https://github.com/openmm/openmmforcefields/blob/637d551a4408cc6145529cd9dc30e267f4178367/openmmforcefields/generators/system_generators.py#L98-L102

So this should be a rather simple upgrade. We'd be happy to have you as the first tester! Thanks @jthorton

[ven828]

Hi, thanks for the reply. Due to confidentiality concerns, I can't share the structures I'm working on at the moment. But I can provide an example PDB such as 1T26 if it can be used to make the adjustments?

[bieniekmateusz]

Thanks @ven828 , I extracted the function to and run this small prototype. I'll try to find some time (most likely next week) to add it as a feature. This will be part of the optimise_in_receptor function.

However, it was point out to me that it may not play with the gnina "scoring function" (@djcole56), so this will have to be accounted for as well. If gnina does not work with cofactors, an error message might be a solution.

Edit: The only changing positions during the minimisation are that of the ligand.

cofactor.zip

[velocirraptor23]

Is the function using cofactors avalaible in the new release (2.0)?