Dear Haddock team,
I have been using a local version of Haddock3 to dock antibody clones that we have partial epitope for. Clone X is shown to share an overlapping epitope with a reference antibody on SPR epitope binning experiments, i.e they block each others binding to the same antigen. Clone Y is shown not to block the reference antibody’s binding, so they potentially share non-overlapping epitopes. Reference antibody has a crystal structure in complex with the antigen, so we know its exact epitope. Inputs for candidate clones are AF3-Rank1 models.
I have done docking runs for the two candidate clones by defining all the CDRs as active and epitope we know from the reference antibody as passive restraints. Since I don’t know the exact epitope for these clones but I know it must be binding somewhere near, I defined all residues on the antigen within 4A of the antibody in the crystal structure as passive restraints.
My aim was to see whether haddock can differentiate the true binding clone vs the non-binding clone, i.e give a more favorable score for the clone that we know binds somewhere near that patch. I’m sharing the results for both clones which I find hard to interpret; it seems the non-binding clone gives similar scores to the binding one. Obviously the most favorable result belongs to reference antibody when I used the true epitope/paratope information.
What kind of docking protocol do you recommend in these kind of scenarios where we have partial epitope information? Or how can i interpret these results ? Please let me know if I need to clarify the situation further. Thanks a lot !