Information-Driven, Ensemble Flexible Peptide Docking Using HADDOCK

  • Cunliang Geng
  • Siddarth Narasimhan
  • João P. G. L. M. Rodrigues
  • Alexandre M. J. J. BonvinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1561)


Modeling protein-peptide interactions remains a significant challenge for docking programs due to the inherent highly flexible nature of peptides, which often adopt different conformations whether in their free or bound forms. We present here a protocol consisting of a hybrid approach, combining the most frequently found peptide conformations in complexes with representative conformations taken from molecular dynamics simulations of the free peptide. This approach intends to broaden the range of conformations sampled during docking. The resulting ensemble of conformations is used as a starting point for information-driven flexible docking with HADDOCK. We demonstrate the performance of this protocol on six cases of increasing difficulty, taken from a protein-peptide benchmark set. In each case, we use knowledge of the binding site on the receptor to drive the docking process. In the majority of cases where MD conformations are added to the starting ensemble for docking, we observe an improvement in the quality of the resulting models.

Key words

Protein-peptide docking Flexibility Information-driven docking Ensemble docking HADDOCK Molecular dynamics simulations 



C. Geng acknowledges financial support from the China Scholarship Council, grant NO. 201406220132. This protocol is adapted from a computer practical offered to our chemistry bachelor students [33].

Supplementary material (1 kb)
All scripts and supplementary material associated with this protocol can be freely obtained from (ZIP 282 kb)


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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Cunliang Geng
    • 1
  • Siddarth Narasimhan
    • 1
  • João P. G. L. M. Rodrigues
    • 1
    • 2
  • Alexandre M. J. J. Bonvin
    • 1
    Email author
  1. 1.Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science—ChemistryUtrecht UniversityUtrechtThe Netherlands
  2. 2.Department of Structural BiologyStanford University School of MedicineStanfordUSA

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