Haddock 2.4 webserver - Protein/Small molecule docking

HADDOCK
1

Dear All,

I have some doubts related to the docking analysis of small moelcules vs Protein.

As my habit from Protein/Protein and Protein/peptide docking analyses, I set true value Sample 180 degrees rotated solutions during rigid body EM to allow the selection of Solvated docking mode.

Consulting the suggested parameters on HADDOCK Web Server - Help I found Sample 180 degrees rotated solutions during rigid body EM set TRUE. Therefore, I ran a second docking analysis with this value and consequently disabling Solvated docking mode. Is this last setting correct? in case yes, is correct to say that solvated docking was removed since solvent molecules can affect the insertion of the small molecule within protein pocket ?

Thank you in advance,

Marian

2

Hi there

I would use the default settings of the server when you are docking ligands.

Solvated docking is not recommended (untested with ligands).

Cheers
Alexandre

3

Thenk you for your rapid answer :slightly_smiling_face:

As for the clustering method, I chose the RMSD and 1.5 angstrom as suggested values ​​for the ligands. In the first run I obtained 40% clustered structures in 10 clusters. Is it correct to rerun docking analysis after increasing the RMSD value until a proper % clustered structures is reached? which % do you suggest as target for a good clustering for protein/small molecule docking?

I supposed to not select too much higher values to avoid the inclusion very different binding poses within the same cluster. Is it correct?

Thank you again.

Marian

4

If you increase the clustering cutoff, models in your clusters will start to be very different. So I would be careful here.

There are no good % of clustering. It all depends on what you are doing and how much information you provided to haddock to guide the docking

5

Thank you.

I followed two cases:

  1. The residues identified by CSM NMR binding sudies as most involved in the binding to the small molecules are set active.
  2. The residues with solvent exposure ≥ 40% are set active.

My idea was to stop at RMSD 2.5 maximum considering the size of the small molecule and how this could lead to an “easy” inclusion of different binding poses in one cluster. Is it correct?

Thank you again again

Marian

6
  1. The residues identified by CSM NMR binding sudies as most involved in the binding to the small molecules are set active.

If you have data this is the most relevant case…

My idea was to stop at RMSD 2.5 maximum considering the size of the small molecule and how this could lead to an “easy” inclusion of different binding poses in one cluster. Is it correct?

Visualise the models within one cluster. Depending of the size of your small molecule 2.5 might be too large already.

The size the clusters does not really matter.

7

Really thank you.

The molecule is less than 6 angstrom, aromatic and with a trifluomethyl group… so I would use the default value and start to inspect the clusters. Does it make sense ?

Thank again

Marian

8

Yes - makes sense - “sense and simplicity” is our motto :slight_smile: