# Small molecule covalent docking **URL:** \ **Category:** HADDOCK\ **Created:** [April 6, 2023, 12:38pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249 "2023-04-06T12:38:02Z")\ **Posts on this page:** 9\ **Page:** 1
**Author:** ![sdraga](https://avatars.discourse-cdn.com/v4/letter/s/b3f665/32.png) [@sdraga](https://ask.bioexcel.eu/u/sdraga)\ **Post date:** [April 6, 2023, 12:38pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/1 "2023-04-06T12:38:02Z")
Hello everyone, 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? Many thanks, S ---
**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\ **Post date:** [April 6, 2023, 12:59pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/2 "2023-04-06T12:59:23Z")
The concept is the same, defining a distance restraint between the atom of your ligand involved in the covalent bond and the cystein sulfur atom I.e. the tutorial is perfectly relevant. ---
**Author:** ![sdraga](https://avatars.discourse-cdn.com/v4/letter/s/b3f665/32.png) [@sdraga](https://ask.bioexcel.eu/u/sdraga)\ **Post date:** [April 6, 2023, 1:08pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/3 "2023-04-06T13:08:13Z")
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? Many thanks! S ---
**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\ **Post date:** [April 11, 2023, 1:19pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/4 "2023-04-11T13:19:23Z")
> 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. ---
**Author:** ![sdraga](https://avatars.discourse-cdn.com/v4/letter/s/b3f665/32.png) [@sdraga](https://ask.bioexcel.eu/u/sdraga)\ **Post date:** [April 12, 2023, 6:23am UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/5 "2023-04-12T06:23:14Z")
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? ![image](https://europe1.discourse-cdn.com/flex013/uploads/bioexcel/original/1X/fd4b6e5db4695f473cb92e7686d5746e5e136deb.png) 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` Thank you very much for you help! Kind regards, S ---
**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\ **Post date:** [April 12, 2023, 6:42am UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/6 "2023-04-12T06:42:25Z")
A visualization issue. 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) ---
**Author:** ![sdraga](https://avatars.discourse-cdn.com/v4/letter/s/b3f665/32.png) [@sdraga](https://ask.bioexcel.eu/u/sdraga)\ **Post date:** [April 12, 2023, 6:53am UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/7 "2023-04-12T06:53:39Z")
Thank you very much, prof. Bonvin! That is, to be honest, what I was hoping to hear! ---
**Author:** ![sdraga](https://avatars.discourse-cdn.com/v4/letter/s/b3f665/32.png) [@sdraga](https://ask.bioexcel.eu/u/sdraga)\ **Post date:** [April 14, 2023, 1:46pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/8 "2023-04-14T13:46:30Z")
Hello everyone, 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](mailto: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’ A solution would be greatly appreciated! ---
**Author:** ![honoratorv](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/honoratorv/32/672_2.png) [@honoratorv](https://ask.bioexcel.eu/u/honoratorv)\ **Post date:** [April 14, 2023, 3:03pm UTC](https://ask.bioexcel.eu/t/small-molecule-covalent-docking/4249/9 "2023-04-14T15:03:07Z")
It seems that you are using `haddock2.2`, I’d suggest you migrate towards `haddock2.4` → [HADDOCK Web Server](https://wenmr.science.uu.nl/haddock2.4)