Protein-ligand docking

HADDOCK
21

Hi Francesca

Did you solve this problem? It indeed seems like CNS should be recompiled.
Search for MAXCP in the various *.inc files in the source directory

22

Hi!
I got 2 Qs!

  1. I want to dock a protein with a non-protein ligand using the web server and I get the error:
    There was an inconsistency in your data
    Error message
    _Second pdb file contains an unknown amino acid or nucleic acid base _
    Make sure to use three letter code for bases and amino acid

Is there any way to make it recognize my ligand?

  1. Is there anyway to automate several docks in a batch mode?
23

Hello,

As indicated here: http://haddock.science.uu.nl/services/HADDOCK2.2/library.html, parameters for co-factors are automatically obtained from PRODRG but they need to be labeled as HETATM in your PDB files.

If you have a large amount of similar docking runs to perform, I would advise to use the file upload interface (http://haddock.science.uu.nl/services/HADDOCK2.2/haddockserver-file.html) that allows you to directly input a HADDOCK parameter file as input instead of filling a complete form.
We do not provide, neither advise, to submit docking runs in a batch mode because of the potential high load that would be triggered on the server. However, you can either use the grid version of HADDOCK (HADDOCK2.2 webserver) or its command-line version running on your own resources, more information here: Bonvin Lab

I hope this will help you,

Best,

Mikael

24

hello everyone Iā€™m so new this docking system I couldnā€™t understand which cluster I need to choose I just dock PRPc and Laminin . Can anyone help me

25

If I understand correctly your question, you docked PRPc and Laminin and you donā€™t know which cluster is the most likely to be correct. Well, with so little insights into your run, I cannot help much.

All the clusters are sorted by HADDOCK score, averaged over the top 4 models of each cluster. All the statistics reported on the results page of the server are also averaged over the top 4 models of each cluster. The HADDOCK score is consistently performing great in blind challenges such as CASP and CAPRI. Therefore, the lower (= the better) the HADDOCK score, the higher is the chance that your cluster depicts the correct binding. But molecular docking is a complex problem and you should always try to confirm your model with extra experiments.

26

Hello,

I have question about the protein-ligand docking on the easy interface:

I am trying to perform a protein-ligand docking and the ligand (histone ligand) contains a chemical modification (acetylated lysine residue). When i try the docking it gives me this error message below:

There was an inconsistency in your data

Error message

First pdb file contains multiple forms of the same residue. This is not supported in the current form. If you would like to supply multiple conformations, please create an ensemble
ATOM 146 CA ALYS A 22 61.012 33.420 37.006 0.50 19.82 C
Directory of the run: http://milou.science.uu.nl/serviceresults/HADDOCK2.2/6331084905/BRPF14
[External Source]

Can you help me figure out what the problem is?

Thank you!
Juliet.

27

Hi Juliet

Two issues:

  1. The error message reports the presence of multiple conformations of some residues in your crystal structure. You will have to select which one to use. This can be done for example with our pdb-tools

See for example in the HADDOCK forum: Haddock server problem

  1. HADDOCK does support a number of modified amino acids, but they need to have the proper naming. The list of supported modified amino acids can be found at:

    https://haddock.science.uu.nl/services/HADDOCK2.2/library.html

In your case, an acetylated LYS should be named ALY instead of LYS in the PDB file

28

I plan to perform docking of ~50 peptides to ~10 receptor PDBs. I installed haddock locally. All the tutorials I come across for local docking mention editing the run.cns file using the online interface. I would prefer to automate that process. Can you suggest what would be the best way to perform multiple dockings with haddock?
Thank you.

29

You can of course launch multiple docking runs. You can probably automate the process and customise your default run.cns to use the recommended setting for protein-peptide docking.

And how to run this will depend on your local hardware and the batch system installed.

30

Hi, could you elaborate more why is it recommended to use guru access to the HADDOCK server for protein-ligand docking?

31

Because as explained in our online tutorials at bonvinlab.org/education you need to tweak some parameter settings and those are only accessible at guru level

32

i see. so if i use prediction interface alone, chances are the results would be unreliable?

33

It all depends on the information at hand, but surely suboptimal

34

Hey, I am having an issue where my ligand is fragmenting during docking. It seems to happen during the it1 phase as the it0 models all seem fine. I am following the recommended settings for small molecule docking. Does anyone know how to solve this?

35

Are you using the web server or a local version?

36

Iā€™m using the web server

37

This is usually happens when something is missing in the topology definition.

Could you elaborate on which ligand are you using?

38

It was this guy: https://pubchem.ncbi.nlm.nih.gov/compound/2145430. I downloaded the 3d structure, converted to pdb format with openBabel and renamed the atoms to make it compatible with Haddock. I did the same thing with the very similar compound: https://pubchem.ncbi.nlm.nih.gov/compound/2222011 and had no issues.

39

We would need more info on what you are doingā€¦ and what your ligand is.

Has the ligand a unique residue number?

40

Is the problem reproducible?