# Using disaccharides as ligand for protein surface docking? **URL:** \ **Category:** HADDOCK\ **Created:** [March 14, 2023, 8:04am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175 "2023-03-14T08:04:29Z")\ **Posts on this page:** 9\ **Page:** 1
**Author:** ![donz](https://avatars.discourse-cdn.com/v4/letter/d/9e8a1a/32.png) [@donz](https://ask.bioexcel.eu/u/donz)\ **Post date:** [March 14, 2023, 8:04am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/1 "2023-03-14T08:04:29Z")
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](https://wenmr.science.uu.nl/haddock2.4/library)). 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?** ---
**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:** [March 14, 2023, 8:30am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/2 "2023-03-14T08:30:08Z")
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?) ---
**Author:** ![donz](https://avatars.discourse-cdn.com/v4/letter/d/9e8a1a/32.png) [@donz](https://ask.bioexcel.eu/u/donz)\ **Post date:** [March 14, 2023, 8:47am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/3 "2023-03-14T08:47:59Z")
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! ---
**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:** [March 16, 2023, 5:50pm UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/4 "2023-03-16T17:50:38Z")
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. ---
**Author:** ![donz](https://avatars.discourse-cdn.com/v4/letter/d/9e8a1a/32.png) [@donz](https://ask.bioexcel.eu/u/donz)\ **Post date:** [March 19, 2023, 8:59am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/5 "2023-03-19T08:59:14Z")
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](https://drive.google.com/drive/folders/1WpJP63eWFuigRfo9zTlVBe7uRm-MXRyw?usp=sharing) ---
**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:** [March 20, 2023, 1:37pm UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/6 "2023-03-20T13:37:37Z")
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. ---
**Author:** ![donz](https://avatars.discourse-cdn.com/v4/letter/d/9e8a1a/32.png) [@donz](https://ask.bioexcel.eu/u/donz)\ **Post date:** [March 21, 2023, 12:09pm UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/7 "2023-03-21T12:09:50Z")
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](https://drive.google.com/file/d/1vvp2LHY6d-dR7Sdnzdn5CxRT05Njx3Sn/view) ---
**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:** [March 29, 2023, 8:44am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/8 "2023-03-29T08:44:07Z")
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 ---
**Author:** ![donz](https://avatars.discourse-cdn.com/v4/letter/d/9e8a1a/32.png) [@donz](https://ask.bioexcel.eu/u/donz)\ **Post date:** [April 1, 2023, 11:51am UTC](https://ask.bioexcel.eu/t/using-disaccharides-as-ligand-for-protein-surface-docking/4175/9 "2023-04-01T11:51:20Z")
Dear Alexandre, Thanks so much for the effort spent and adding the alpha-1-1 linkage. It seems that we can now succesfully load the trehalose as a glycan and can try to dock it to a protein’s surface!! I’ll let you know once we (hopefully) made some progress 😃, or when we run into issues 😅! Have a great weekend. Best regards, Daan