Active residues for only one protein binding partner


I am attempting a docking run of a protein complex for which I have a crystal structure (partner A) and an AlphaFold structure for a domain which is not present in the crystal structure (partner B). For partner A, I have some possible active residues identified by hydrogen-deuteriem exchange (HDX) experiments. The regions most protected from HDX are my proposed active residues for the docking.

My problem is that I have no information about the active residues on partner B. The HADDOCK2.4 web server requires either active residues for both partners or for neither, so only having one set of active residues is not compatible with this type of docking. I can attempt the run with no active residues, but I predict that this will be computationally expensive. I have seen some advice that I could define the whole of partner B as active residues, but this was in the context of protein-peptide binding and I think the 101aa partner B is perhaps too big for this to work.

Does anyone have any advice for how to get around the need for both partners to have defined active residues? I currently have expert access. Thanks in advance!

The 2.4 server has the option to define all solvent accessible residue as passive.
This is what you should try for molecule B.

But do increase the sampling then to say 10000/400/400 for the various stages of HADDOCK.

Also do check your alphafold model and remove any disordered region. It doesn’t make sense to include those for the docking.