Best practice for heparin docking?

HADDOCK
1

I have seen a couple references to this, but I’m not sure the best way to go about it. I don’t think I should set up heparin as a ligand, which I have done with a simple DP4. It seems as though I should link glycans but not sure of the best way to go about it? I didn’t see a lecture file based on the glycan docking but maybe I am missing one.

2

Hi,

Setting up heparing as a ligand is likely the best choice, as it is typically highly sulfated and we currently have no support for sulfonated glycans (the list of supported ones is here HADDOCK Web Server - Settings). See for example this topic Recognition problem after glycan sulfation

For supported glycans there is a new tutorial describing the best docking protocol (in that case using HADDOCK3): Protein-glycan modelling tutorial using a local version of HADDOCK3 – Bonvin Lab

Cheers,
Marco

3

Thanks for your help. After some mistakes, I have finally figured out how to set up my heparin molecules as a single ligand. However, heparin typically takes on the repeating form GlcNS6S-IdoA2S etc, in the literature. While this is the major disaccharide unit, the minor units make a difference, so I made some new files with 3S sulfation and +/- NS and 6S and replacing the IdoA2S with either IdoA or GlcA. Is it legitimate to compare the HADDOCK scores I get from the various sulfated samples I made to suggest which ones might bind better an therefore which sulfation sites are important?

4

Hi! Glad to hear you made it!

The HADDOCK score is not a proxy for binding affinity, but better scores could be indicative of a preference of binding (see also Compare HADDOCK scores - #2 by amjjbonvin)

The rule of thumb here is that the more the system remains constant the more sense it makes to compare the HADDOCK scores. What we typically suggest in this case is to take an example in which you know the answer (e.g. two molecules with different minor units in which you know the binding preference in your case) and test if you can tell the difference from the scores.

PS: remember that this forum is searchable, lots of discussions about comparing scores can be found :wink:

Cheers,
Marco