HADDOCK result problem

[Donia]

I apologize for the number of questions I’ve been asking. I completed a protein-peptide docking using HADDOCK. The protein I used has a ligand (ATP) bound to it, and I uploaded the corresponding PDB file.

However, when I analyzed the results from the best cluster, I noticed that in clusters 1-4, the ATP was no longer bound to the protein, although the peptide remained bound. Interestingly, this issue did not occur in clusters 1-1, 1-2, and 1-3.

Could you please help me understand why ATP was separated from the protein during docking, and how I might resolve this issue? I have already redone the docking, but the problem persists.

[amjjbonvin]

This is very strange.

But is the ATP binding site any close to the ATP? If not then I would not worry about it.

Alternatively you could define some distance restraints to keep the ATP in place

[Donia]

it is my first time to make Molecular Docking. could you please tell me how can i define some distance restraints to keep the ATP in place?

[amjjbonvin]

Check for examples the following publications:

• R.V. Honorato, M.E. Trellet, B. Jiménez-García1, J.J. Schaarschmidt, M. Giulini, V. Reys, P.I. Koukos, J.P.G.L.M. Rodrigues, E. Karaca, G.C.P. van Zundert, J. Roel-Touris, C.W. van Noort, Z. Jandová, A.S.J. Melquiond and A.M.J.J. Bonvin. The HADDOCK2.4 web server: A leap forward in integrative modelling of biomolecular complexes. Nature Prot., Advanced Online Publication DOI: 10.1038/s41596-024-01011-0 (2024).

• A.M.J.J. Bonvin, E. Karaca, P.L. Kastritis & J.P.G.L.M. Rodrigues. Correspondence: Defining distance restraints in HADDOCK. Nature Protocols 13, 1503 (2018). Free online only access

And also for example this tutorial:

https://www.bonvinlab.org/education/HADDOCK24/HADDOCK24-Xlinks/#scenarios-for-docking—how-to-make-use-of-ms-data-in-haddock

You will have to measure a few distances between specific atoms of ATP and some protein atoms.