ERROR: Solvated peptide-protein docking keeps failing

HADDOCK
1

Hi,

I’m trying to dock an 8-mer peptide to a small PDZ domain (82 residues) and I’ve been trying to perform a solvated dock and refine with a short MD in explicit solvent (water). I’ve tried several times and did different things, but every time I get the following error:

Status: Failed

Status: FAILED There was an error in the water refinement stage of the docking. The partial run can be downloaded as a gzipped tar file here. For more information, check the following CNS output files for error messages: [complex_run1_1w.out]. If you are unsure how to correct the error, visit the HADDOCK website, check out the HADDOCK discuss group, or send a mail to haddock.support@gmail.com. The output of HADDOCK is [here]. The file containing your docking parameters is [here].

Your HADDOCK run stopped because of the following error:

             ^^^
     %CHAIN-ERR: unrecognized command:
     ATOM    856  H2
                  ^^
     %CHAIN-ERR: unrecognized command:
     ATOM    856  H2  WAT
                      ^^^
     %CHAIN-ERR: unrecognized command:
     ATOM    856  H2  WAT   472
                            ^^^
     %PARSER error encountered: Encountered too many parsing errors.

I’m not sure what this means, how to fix it, or what I’m doing wrong. I would greatly appreciate any help/suggestions.
Here are my job parameters and what I’ve tried:

  • Protein (PDZ domain): 82 residues - no strange residues or PTMs
  • Peptide: 8 residues - no strange residues or PTMs
  • I select active and passive residues based on experimental structures in published papers.
  • I remove all HETATMs and HOHs from my files before docking.
  • I checked my PDB files with PDBTOOLS (pdb_validate) and PyMol - no obvious errors or issues.
  • I added hydrogens and removed hydrogens (both polar and nonpolar) to both PDZ and peptide - still fails with the same error.

Docking without solvation works. The jobs only fail when I toggle “Perform solvated docking” on, but I would really like to try and see if it makes a difference and even refine with short MD in explicit solvent (water).

Let me know if I missed something in my protocol or if you need more info about my jobs! I’m fairly new to docking and HADDOCK, so very keen to learn. Also, I’m using the web server.

2

do you have a run ID to share?

3

Thank you for responding. Sure, any of these …

  • 488630
  • 488859
  • 490553
  • 490554

Please let me know if you need anything else.

4

I can reproduce the problem.

But it does not occur with other systems I just tested.
So something goes wrong with your particular system. Must be related to your input structures.

Note that not all models are failing. If you download the archive of the full run you can still find models in the water directory.
The flexible refinement (it1) has completed fine.

5

Thank you very much for letting me know! I’ll have a look at archive of the full run to see if I can use some of those models.
Do you perhaps know, or can you give me an idea of what might be the issue with my input structures? I’ve tried to run checks but no errors came up which is why I posted the issue here.

6

Difficult to say… It is only a few models failing.

You could eventually try to run first your input PDB via the refinement server of HADDOCK.

7

Thank you. So, using the refinement server, I could maybe first try to energy minimise to maybe stabilise the structure and/or combined with the water refinement option?

8

Run the default protocol I would say

1 Like
9

Thank you very much, @amjjbonvin!

I’m just leaving some extra details here for anyone who might encounter the same issue …

I used the HADDOCK webserver’s Refinement server and first tried the energy minimisation refinement and then (separately) the water refinement (default) protocol (as @amjjbonvin suggested). The EM refined structure gave the same error as previously, so it didn’t work. But the default water refinement structure worked - no errors.
I submitted my protein starting structure for water refinement and used the refined structure in my next 2 docking jobs: in the first job, I only selected “Perform solvated docking” and in the second job I only selected “Refine with short molecular dynamics in explicit solvent”. Both of them worked and the jobs finished successfully. Hope this helps!

10

Excellent - problem solved.

And thanks for documenting it!