Protein-Protein Interaction

Hello everyone,

Hope you are in good health.

I am a biologist and would like to research on the interaction between two proteins using in silico approaches.

My project involves attachment of a ligand to protein and interaction this complex to another protein. In fact, this project has two phases.

First, I need to calculate the binding energy between Protein-Protein interaction (Phase I), next, make a complex of Protein-Ligand (using Auto Dock 4.2) and study on the attachment of this complex to another protein (Phase II).

Finally, I should compare the Phase I and II.

As far as I know, we cannot do a docking simulation of Protein-Ligand / Protein using most docking website servers.

Could you please tell me how to perform these docking? Or if there is any docking web server or software to perform this docking simulation? I mean (Ligand-Protein)/Protein interaction.

Thank you in advance,



Haddock is able to do multi-body docking, please check the tutorials on our website:

Good luck with your project. :slight_smile:

Simply give your protein-Ligand complex as one molecule to haddock and the second protein as the second molecule.


  • the ligand must have a unique residue number not overlapping with the protein and must be defined as HETATM in the pdb file.

Dear Prof. Bonvin,

I would like to thank you so much for such a detailed answer.

According the answer you had provided, I prepared a pdb file of protein and ligand, and defined ligand as HETATM atom with a unique residue number (576). Unfortunately, this error comes up after loading the pdb of complex as molecule 1.

"Error in PDB file. Your PDB contains multiple residues with number 576 in chain"

I have been trying hard to fix this problem for two days.

Could you please tell me what I should do?



The error tells you that another residue 576 exists in the same chain (molecule), did you check that?

Search for all instances of residue 576 and also make sure all atom names in it are unique

I checked all atom names and residue number. Everything looks OK.

Unless I delete the ligand from the PDB file, I cannot go on to the next step (input parameters).

Please tell me what this error is.

" Error in PDB file. Your PDB contains multiple residues with number 576 in chain.

ATOM 8752 H1 DRG X 576 32.821 30.233 1.368 1.00 20.00 rece H (Offending Line)


ATOM 32 N ARG 3 11.281 86.699 94.383 0.50 35.88 N (Example Valid Line) "

Note: DRG is the name of ligand

Thank you in advance


How can you expect any answer without sharing your PDB file…?!

I am attaching the pdb file of protein + ligand.
Could you please take a glance and let me know your opinion.
Thankscomplex.pdb (678.9 KB)

This is not the file that gave you the error message. The ligand is number 550.

But the error will also happen with this file since you have two atoms called H1 in the ligand….

I.e. not unique atom names.