Using disaccharides as ligand for protein surface docking?

HADDOCK
1

Dear all,

I’m doing experimental work trying to determine minimal protein-excipient ratios for sufficient protein stabilization upon freeze drying and storage at elevated temperature, e.g. 50-60℃ storage). I’m trying to use HADDOCK to simulate the potential interaction potential of excipients with several protein’s surface and see if this can be related to experimental data.

Currently looking at several proteins: OVA, BSA, beta-galactosidase, MIF
And several excipients: trehalose, arginine, a yet to be determined trisachharides.

However, this is where I run into issues. An arginine pdb generated with Avogadro works just fine. However, a trehalose pdb is not accepted.

The HADDOCK library shows only monosaccharides that are supported.(HADDOCK Web Server - Settings). Trehalose is essentially two 1-1 linked alpha-D-glucopyranose (GLC) units, which is supported as monosaccharide.

Is there a way to use disaccharides as ligand?

2

Did you define your trehalose as a two residue glycan (i.e. two GLC units, each with a different residue number)?

But we might not have the 1-1 linkage defined (is that a beta-1-1 link?)

3

Thanks for your feedback, much appreciated.
This was also just suggested by a colleague who has experience with HADDOCK; he was pretty sure it would work. Still, I raised the same concern to him, since the linkage would impact the molecular geometry. It is a 1–1 alpha bond that links the two GLC units!

4

It doesn’t look like we have support for alpha-1-1 linkages…

Do you have a PDB file of your glycan you could share?
We can see if we can easily add it.

5

Thanks again, for taking the time to help me.

I cannot upload a file directly to the forum as I’m a new user. However, I supplied a google drive link with 2 PDB files, i think the one that might be suitable is the trehalose_LIG.pdb. I really hope you can add it!

Best,
Daan

https://drive.google.com/drive/folders/1WpJP63eWFuigRfo9zTlVBe7uRm-MXRyw?usp=sharing

6

Sorry - but your files have ambiguous atom names (all carbons are name C, oxygens, O, … Search GLC residues in the PDB and check the atom nomenclature. This is the atom naming you should follow in your trehalose (which consists of two GLC units).

I don’t have time to do all this renaming for you.

7

Sorry about that, we extracted a trehalose pdb from a 5dx9 structure, it should be named correctly now. See attached, does that look usable?

Best,
Daan

trehalose_2GLCresidues.pdb - Google Drive

8

The alpha 1-1 linkage should now be supported on the 2.4 server. Please give it a try and let us know if it now works properly for you