I’m running a small ligand docking into a protein. I have chemical shift perturbation which I already converted into the active residues for protein. Also, I defined the whole molecule of small ligand as active residue. Then I submitted the job using the Easy Interface. I got the error message as :
TOTAL NUMBER OF DISTANCE RESTRAINTS FOR RIGID BODY DOCKING IS ZERO!
CONTROL YOUR PARAMETER SETTINGS AND RESTRAINT DEFINITIONS
STRUCTURE NUMBER 61
what should I do? I also sent email to register ID for guru interface, but haven’t been responded yet.
First we did not receive any email about your guru request.
Second, check your active residues definitions.
Could be you entered the wrong residue number for the ligand for example… Clearly the restraints you defined are not recognised.
Thank you, I only have chemical shift perturbation on the protein, so I accordingly defined active residues on protein. But for ligand, I don’t have much specific information, so I just set the whole small molecule as active residue. Is this ok?
Yes - simply define the entire ligand as active for HADDOCK - BUT only if you are speaking of a small molecule ligand.
If you “ligand” is another protein, then rather define all solvent accessible residues as passive (and increase the number of models generated at it0)
You can for example use the NACCESS software to calculate accessibility or the freely available freesasa (see http://freesasa.github.io)
See the related topic on the HADDOCK manual pages at:
http://www.bonvinlab.org/software/haddock2.2/generate_air_help/#filter
thank you. For current, I only want the small molecule docking. I just got a run successfully finished. It did it0 with 990 structures and definied only 1 cluster
HADDOCK score -16.6 +/- 7.7
Cluster size 199
RMSD from the overall lowest-energy structure 0.8 +/- 0.5
Van der Waals energy -25.1 +/- 2.1
Electrostatic energy -14.9 +/- 7.5
Desolvation energy -11.6 +/- 2.9
Restraints violation energy 229.9 +/- 51.31
Buried Surface Area 521.5 +/- 10.7
Z-Score 0.0
The top 4 structures selected present very different orientations of the small molecule in the pocket. I hope to use the guru interface for more options i.e. flexible docking. Could you give some suggestions?
I think I will follow part of parameters for the flexible docking used in the example http://www.bonvinlab.org/education/HADDOCK-binding-sites/#preparing-pdb-files-of-the-ligands-for-docking .
One issue remains: I tried to register on the webpage or sent email for the permission to use the guru interface, but didn’t get passed, could you help me on this?
Did you decrease the clustering cutoff? For ligand docking, better to use RMSD cluster with a cutoff of 2A max.
Thank you. Using the guru interface I changed clustering rmsd cutoff to 2A and it comes up with better converging result. So, usually the Cluster 1 with the best score should be more reliable?
To analyze the result, is there any tool in the package available to define the residues interacting with the ligand, for example sorting by distance? I hope to get some SAR clues how the residues in the pocket contribute to the ligand binding.
You can use in the local installation of HADDOCK the contacts program to list all intermolecular contacts within a given cutoff. This is the same program used in our online protein-ligand tutorial
Thanks. I went into the /Structure directory and applied contacts-analysis.csh, it generated the /contacts folder and contacts file for each complex. But when I applied contacts-statistic.csh outside of the contacts directory, it returned to me: foreach: No match. And the Acontacts.lis file is empty. How to fix this?
Did you follow the instructions from out tutorial?