# Haddock: S-C bond broken after docking

**URL:** <https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424>\
**Category:** HADDOCK\
**Created:** [February 16, 2025, 12:02pm UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424 "2025-02-16T12:02:02Z")\
**Posts on this page:** 5\
**Page:** 1

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**Author:** ![joana.santos](https://avatars.discourse-cdn.com/v4/letter/j/7feea3/32.png) [@joana.santos](https://ask.bioexcel.eu/u/joana.santos)\
**Post date:** [February 16, 2025, 12:02pm UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424/1 "2025-02-16T12:02:03Z")

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Hi!

I am trying to dock an antibody-drug conjugate (ADC) to a protein. In the pdb file with the antibody-drug conjugate I have a modified cysteine (CYC) connected to my ligand with a 0.8 A bond.  
In the complexes that I get after the docking, the ligand from my ADC has moved far away from the antibody and the bond is not there anymore.  
Here is the link for my run [HADDOCK results page](https://rascar.science.uu.nl/haddock2.4/result/4101165020/445131-Docking_ADC1_08_160225)

I tried connecting my ligand to a different cysteine before and the docking of the ADC with the protein worked well, however this time my ADC had its ligand in the terminal cysteine, so I believe it is not staying connected due to the higher repulsion of the terminal cysteine.

Is there any way to solve this?  
Thank you in advance.

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**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:** [February 17, 2025, 9:02am UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424/2 "2025-02-17T09:02:31Z")

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Dear Joana

A few points:

1. The covalent bond won’t be maintained. You should add some distance restraints to keep it.

2. Your ligand seems very remote from the binding site, i.e. it does not matter 🙂 You can always put it back by superimposition

3. You should define the antibody+ligand PDB file as “protein-ligand” when submitting it. In that way a few distance restraints should be automatically defined (but not the bond to CYC which you need to provide as a separate unambiguous file.

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**Author:** ![joana.santos](https://avatars.discourse-cdn.com/v4/letter/j/7feea3/32.png) [@joana.santos](https://ask.bioexcel.eu/u/joana.santos)\
**Post date:** [February 17, 2025, 1:52pm UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424/3 "2025-02-17T13:52:43Z")

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Dear Dr. Bonvin,

Thank you for the answer.  
I tried using a distance restraint between the carbon and the sulphur, however it is not working.  
I wrote:  
assi (resid 215 and name C17 and segid A) (resid 215 and name SG and segid A) 1.7 1.7 0   
I wanted the bond to stay with 1.7 A, however it still moved away.

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**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:** [February 17, 2025, 2:25pm UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424/4 "2025-02-17T14:25:34Z")

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Your CYC is residue 214… and not 215 based on what I see in a cluster PDB file

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**Author:** ![joana.santos](https://avatars.discourse-cdn.com/v4/letter/j/7feea3/32.png) [@joana.santos](https://ask.bioexcel.eu/u/joana.santos)\
**Post date:** [February 18, 2025, 8:57am UTC](https://ask.bioexcel.eu/t/haddock-s-c-bond-broken-after-docking/5424/5 "2025-02-18T08:57:10Z")

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Sorry, my mistake. It worked now. Thank you.