I would like to perform covalent docking of a small molecule to a cysteine residue on my receptor. I had a look at the covalent docking tutorial, but there are some differences between re-docking a ligand based on a crystal structure and de-novo covalent docking.
Based on my limited understanding there should be some additional chemical modification to the ligand as well, in order to facilitate covalent bond formation.
Could you perhaps point me towards a tutorial that would cover such a case for HADDOCK?
Thank you, prof. Bonvin! So just to make sure I understand - there should be no additional chemical modification to the ligand structure (as is the case with other docking software)?
Also, would like to ask if it would be possible to dock the resulting protein-covalent ligand complex to another protein, in order to assess effects on the protein-protein complex formation?
Thank you, prof. Bonvin! So just to make sure I understand - there should be no additional chemical modification to the ligand structure (as is the case with other docking software)?
Indeed - but no atoms will be deleted, i.e. if some should not be present once the covalent bond is formed they should not be in your starting structure
Also, would like to ask if it would be possible to dock the resulting protein-covalent ligand complex to another protein, in order to assess effects on the protein-protein complex formation?
In principle yes. But the covalent bond will not be really present. Also the ligand should be redefined as HETATM for HADDOCK submission.
It works, thank you! My only concern now is the fact that there appears to be a additional bond between the cys residues and an additional carbon on the ligand. Does this look right?
My CNS restraint file contains only the following line, perhaps I missed something here?
assign (segid A and name SG and resi 156) (segid B and name C11 and resi 1) 1.8 0.1 0.1
But you can probably improve your docking by defining a second distance restraints to the C12 atom to enforce a better angle (if you know what the angle should be - the corresponding distance could be estimated for example from a CYS by measuring the SG - CA distance)
I am trying to resubmit the docking using the Guru interface for covalent protein-ligand docking (which worked wonderfully the previous time) but get the error message:
There was an unknown problem in the parsing of your data.
This is either a server error, or some inconsistency in your input has been detected that was not properly reported.
Please save this page from your browser as HTML and email it to haddocking@gmail.com.
Importantly, do provide the following information:
Which interface are you accessing?
What is your access level to the HADDOCK server?
What kind of molecules are you docking?
The HADDOCK server is in constant development, thank you for your patience.
Full error information:
Traceback (most recent call last):
File “/home/enmr/services-enmr/HADDOCK2.2/py/haddockserver.py”, line 179, in serve_haddock
covproject = webform[‘covid’].value
File “/usr/lib64/python2.7/cgi.py”, line 540, in getitem
raise KeyError, key
KeyError: ‘covid’
