I am using HADDOCK version: 2.4 - May 2021 release on the Ubuntu server. I am trying to run Ab-Ag HADDOCK tutorial (Ambrosetti, et al BioRxiv, 2020) locally. The tutorial creates Ambiguous Interaction Restraints (AIRs) using HV loops as active residues against antigen residues within 9Å from the antibody in the complex reference structure, filtered by their solvent accessibility, as passive. However, I wonder if it is possible to use HV loops as passive, as well. I want to use HV loops as passive because of the energy penalty as you described here:
“The distinction between active and passive means that an active residue not at the interface (defined as the union of active and passive residues of the partner molecule) will result in an energy penalty while this is not the case for passive residues.”
The script which writes the AIRs (active-passive-to-ambig.py) needs at least 1 active residue and it writes AIRs with 2.0 Å. In the other tutorial (Tutorial describing the use of a local version of HADDOCK2.4), the restraints are created as “more specific only between CA-CA atoms and with slightly increased distances to 3.0 Å” for HV loops as active residues against solvent-accessible residues on antigen as passive. Consequently, at the Cluster-based analysis of the docking results, it is said:
“Between 8 and 9 restraints are violated on average in this example, out of the 28 AIR restraints we defined. Remember that our definition of active residues in the antibody was based on predicted CDR loops and might not be perfect.”
Is it logical to use AIRs using residues on HV loops as passive against passive residues on antigen protein, with 3.0 Å or longer distance? Is there any possible way to use AIRs if we do not have any active residue but have only passive residues. What do you suggest about using AIRs from passive-to-passive residues?
Thanks in advance.