Amyloid-peptide docking, structure blown up

1

Dear all,

Thank you for spending time reading this post. We have used HADDOCK to do amyloid-peptide docking for some time. It worked very well in the past.

However, we recently encountered a case that sometimes the amyloid structure was completely blown up after docking. Like this:

bad
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The amyloid structure is completely the same in both pictures, but the peptide adopts different conformations. Is there something wrong with our amyloid structure that causes this strange result? Is there any special operation done in HADDOCK that we should be aware of?

Many thanks!
Best regards,
Muhui

2

How did you setup your docking? How many molecules defined as separate entries?

And local or server?

3

We used the server, uploaded the pdb files and selected the region to be docked. The amyloid pdb contains 8 peptides, and we set it as a protein. The other peptide pdb contains only one peptide, and we set it to a peptide. All other parameters are kept as default. Many thanks!

4

Can you provide a link to the problematic run?
(or email it)

5

Here is the link:
HADDOCK results page (uu.nl)
Thank you!

6

Not all models are “blown” up - if you download the full run and look at the top model in the structures/it1/water directory (check file.nam for the ranking) it looks normal. But many models are indeed problematic (and your clustering is poor).

This happens during the flexible refinement, which could point to a problem with your amyloid model (e.g. bad geometries and internal clashes).

You might try to refine first the model via our refinement interface (haddock2.4 server) which also works for single structures.

See the result at: https://bianca.science.uu.nl/haddock2.4/run/1111111111/85076-amyloid

(note that for that to work properly your PDB file should contain a chainID (a feature we need to fix).

7

Got it! I will try again after refining the structure. Thanks again!