Error while doing the HADDOCK ligand binding site tutorial

I am very new to the the system so I tried to do the tutorial and I when i was finished i submitted but later found that i had to define my active/passive residues but there was no mention of the information i need to put there, Is there an option that the system automatically puts in that needs to unchecked or did i miss something whilst doing the tutorial?

And a further question, I have tried to dock a ligand to a protein but when i provide info for the active site for the protein, i need to define the active residues of my ligand but what should I write? If I write the same residues as my protein it gives me an error saying that ‘manual restrains and random patches are mutually exclusive’. If I leave them both empty it says that I need to at least define active/passive residues for one molecule but that doesn’t make sense since I would have done that during the first run.
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Hi Dan

In the first stage of that tutorial you don’t need to define active or passive since we are using instead random patches as restraints:

 Step 4: Turn on random surface restraints. For this unfold the Distance restraints menu:
 Define randomly ambiguous interaction restraints from accessible residues -> Check the box

You only need to define active and passive in the second stage.

So if the server complains about missing info, it means you did not follow all instructions in the tutorial.

As for defining the active residue for the ligand, simply give its residue number.

I tried again and the same error occurred, it might be because i don’t have access to the guru level, if possible could you send me a link/email to apply for access if i don’t already have it


Please send a direct email with your username / email

just ran into another slight problem,

My docking runs have been in queue for more than 2 days whereas previously it only took around 6 hours for results. Is this due to a backlog in the web server or is there something wrong with the parameters/components.

The only difference between these runs and my previous is that I included water molecules relevant for the interaction.

Indeed a glitch in our post-processing scripts. Should be fine again.
Sorry about that

I am now trying to dock two ligands at the same time using a linker between them but the docking results show that they haven’t docked but it worked on one example where I changed some of the docking parameters but I can’t remember the specifics. How should I continue? I can provide a link that worked and one that didn’t example that worked didn’t work

The question is: What did you do differently?

You probably need to define the linker as fully flexible.

But a better approach is probably to cut them in two - perform a three body docking with a distance restraint between the ligand to restore the linkage. Kind of our FMB protocol - see:

E. Karaca and A.M.J.J. Bonvin A multi-domain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes. Structure, 19 555-565(2011).

Hi Dan,

right now I am studying about this, and find some problem with you before. can you tell me how to fixed it?
I just want to docking a protein with a ligand, but there is an error said that “Manual restraints and random patches are mutually exclusive”.
thank you

“Manual restraints and random patches are mutually exclusive”

What can I say more… You can not define restraints and at the same time apply random patches…

oh okay Prof, I found it the solve, its because I need to elevate my access level.

but Prof I have another problem.
I still have a problem with my ligand, I get the pdb file from pubchem (pentamidine drug), its directly structure of drug, it not from a protein like you show in the tutorial. but my running is error because they said that my second pdb file contains an unknown amino acid or nucleic acid base UNK. what should I do? do I need find pentamidine in some protein structure as a ligand?

You have to define it as ligand in the server

I did it Prof, but it doesn’t work.
here I attached link of my reference journal Pentamidine inhibit S100A4 - p53 interaction and decreases cell proliferation activity - PubMed.
thank you

This literally means that your PDB has an UNKNOWN position, we cannot simply guess what aminoacid/nucleic base it it. If you are using a structure taken from the PDB database, this most likely means that there is not enough information to determine which aminoacid/base is at this position. That being said, is this UNKNOWN position relevant to your docking, is it in or near the binding site? If it is in a region far from your binding site, you could just delete this unknown residue (by editing the .pdb file) if you are not sure if this is important or not, you should apply homology modelling and get a more complete model.

We can try to help you but your questions are not related to HADDOCK itself but to the pre-processing of your input models, good luck!

“it does not work” is not a description of the problem we can help with…

More details required, exact error message…