Protein-Protein Docking: HADDOCK, ClusPro and What Free Tools Can Do

By BioDockify Computational Research Team · October 11, 2026 · Tutorials

Protein-protein docking from zero: why docking two proteins is harder than protein-ligand docking, how HADDOCK restraints and ClusPro clustering work, where AlphaFold-Multimer fits, the CAPRI benchmark reality, and a practical free-tool workflow.

Read the complete article with tables, code and references on BioDockify.

Key References

• Dominguez, C., Boelens, R. & Bonvin, A.M.J.J. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J. Am. Chem. Soc. 125, 1731-1737 (2003). DOI: 10.1021/ja026939x
• Comeau, S.R., Gatchell, D.W., Vajda, S. & Camacho, C.J. ClusPro: an automated docking and discrimination method for the prediction of protein complexes. Bioinformatics 20, 45-50 (2004). DOI: 10.1093/bioinformatics/bth148
• Lensink, M.F., Nadzirin, N. & Velankar, S. Protein-protein interfaces: CAPRI 50 rounds and beyond. Nat. Methods 17, 945-952 (2020). DOI: 10.1038/s41592-020-0956-x
• Evans, R., O'Neill, M., Pritzel, A. et al. Protein complex prediction with AlphaFold-Multimer. bioRxiv (2022). DOI: 10.1101/2021.10.04.463034
• Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583-589 (2021). DOI: 10.1038/s41586-021-03819-2

Scope & Limitations

Free tiers of docking servers impose queue limits and confidentiality constraints inappropriate for unpublished proprietary complexes Predicted interfaces without any experimental or evolutionary restraint remain the hardest docking class; treat confident-looking interface models as hypotheses