What does "Define passive residues automatically around the active residues" mean?

HADDOCK
1

I don’t know much about HADDOCK. I see that many examples have ticked “Define passive residues automatically around the active residues”. What does it mean if this option is not ticked? Is it feasible?Thanks!

2

I don’t know much about HADDOCK. I see that many examples have ticked “Define passive residues automatically around the active residues”. What does it mean if this option is not ticked? Is it feasible?Thanks!

Because the info you might have to define the binding site is never really perfect, this option will select as passive residues all surface neighbours of our active residues.
It effectively increases the defined interface.

But the passive residues are not penalised if not in the interface during the docking, while active are.

You can turn it off, but you must be very confident that both interface you are defining are the correct ones.

1 Like
3

Am I understanding this way? If there is a docking structure in which the ligand is in contact with residues other than the active residue, but if I don’t check this option, there will be no penalty for interacting with this non active residue. But if I check this option, this residue will be regarded as passive residue and then punished, so that the HADDOCK score of this structure will be lower. So, this will increase the score difference between the correct ones and the wrong ones (in contact with the non active residue), otherwise the score difference between them will become smaller.

4

Consider an example with protein A and protein B:

For protein A it has been shown that residue 10 is involved in the interaction, but this evidence is not very strong.
For protein B you are 100% sure that if residues 42 and 87 are not participating in the interaction, the interaction does not occur.

The restraints could be defined such as:

Protein A active: 10     / automatically define passive = Yes
Protein B active: 42, 82 / automatically define passive = No

What will happen is:

  • if there is an interaction between protein A residue 10 and protein B residue 42 or 82 it will be scored favourably.
  • if there is an interaction between protein A by a residue close to 10 and protein B residue 42 or 82 it will not be penalized.
  • if there is an interaction between protein A residue 10 and and a residue in protein B that is not 42 or 82, it will be penalized.

You must then understand how this best fits your scenario.

1 Like
5

And probably a good idea to read (again) our JACS 2003 original HADDOCK paper.

1 Like
6

I just read this paper, combined with your reply, I find that my understanding is just the opposite of the software settings. Passive residue is not a residue that does not participate in binding, but an extension of active residue, which can effectively increases the defined binding interface.

Thanks a lot!

[Definition of active and passive residues in HADDOCK 2003 JACS:
We distinguish here between “active” and “passive” residues. In the case of NMR titration data, the active residues correspond to all residues showing a significant chemical shift perturbation upon complex formation as well as a high solvent accessibility in the free form protein (>50% relative accessibility as calculated with NACCESS).

The passive residues correspond to the residues that show a less significant chemical shift perturbation and/or that are surface neighbors of the active residues and have a high solvent accessibility (>50%).]

7

Thank you very much for your careful reply, and explain clearly the application scenarios of this option. I think I understand the meaning of this option now, thank you!

1 Like