Haddock generatong only one cluster

HADDOCK
1

Hi,

I wanted to confirm a small detail. I used haddock 2.4 web server to perform protein-ligand docking for different compounds and used different parameters as well. Every time Haddock has generated only one cluster. Is this the way software is now or is there something I am missing while doing the docking?

Thanks in advance,

Vibes

2

Dear user,

No, HADDOCK2.4 is not producing only one cluster.
This behavior must come from your clustering parameters.

  • What sampling did you do ? (at it0, it1, itw)
  • Do you use the RMSD clustering ?
  • What threshold did you use ?
  • What is the value set for Minimum cluster size ?

Also, if your restraints are very focused, it can be that only one cluster is generated, containing all the models.
If not, the Minimum cluster size could be a limiting factor, as if a cluster is composed of less than 4 models, it is not considered as a cluster.

Cheers

3

Hi,

I used 2000/400/400 for it0, it1 and itw respectively. I used RMSD clustering and set the total number of structures to analyze to 400 as well. I tried ab-initio modelling, without providing any restraints as well and it generated only one cluster in that case too. Should I change anything in my parameters? Also, the number of clusters generated has no bearing on the validity of the results right? As the top cluster is the most accurate one?

Cheers

Vibes

4

Can you share the link to your results page?

6

Looking at random non-top-ranked models from “VI-9-4C1_conf_3 run”, I suspect that what happened is that ab-initio restraints, in this case are the centre of mass (COM) restraints, did target two sides of the protein, spesifically one where all top-ranked models are bound (let’s call it the 1st pocket), and the opposite side (around amico acid 50, let’s call it the 2ns pocket).

Looking at the scores of those models, the ones in the 2nd pocket have very high AIR violation - consequently, only models in the 1st pocket made it to it1 and forward. So the final output is biased by the COM restraints.

What you can try is to turn off the "Use tight center of mass restraints?” - see if this will yield more than 1 cluster. If this run will result in single cluster - then center of mass restraints are not suitable for this docking case

7

Thank you very much for your reply. I have not used centre of mass restraints for any run other than the abinitio run, yet I have got single cluster as the output. I tried to replicate a published procedure by Bonvin lab and still got a single cluster as the output.

Thank you in advance.

Vibes

9

Hi,

Since the active site of this enzyme is clearly defined, I use that to define my restraints between the ion and residues in the active site. I will work on your suggestion and make the residue 138 and 229 passive and dock again.

Thank you very much for your inputs.

Vibes