Cited by 3,187Protein Structure and DynamicsEnzyme Structure and FunctionComputational Drug Discovery Methods

HADDOCK: A Protein−Protein Docking Approach Based on Biochemical or Biophysical Information

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Dominguez, Cyril, Boelens, Rolf, Bonvin, Alexandre M. J. J.·2003·Journal of the American Chemical Society

Abstract

The structure determination of protein-protein complexes is a rather tedious and lengthy process, by both NMR and X-ray crystallography. Several methods based on docking to study protein complexes have also been well developed over the past few years. Most of these approaches are not driven by experimental data but are based on a combination of energetics and shape complementarity. Here, we present an approach called HADDOCK (High Ambiguity Driven protein-protein Docking) that makes use of biochemical and/or biophysical interaction data such as chemical shift perturbation data resulting from NMR titration experiments or mutagenesis data. This information is introduced as Ambiguous Interaction Restraints (AIRs) to drive the docking process. An AIR is defined as an ambiguous distance between all residues shown to be involved in the interaction. The accuracy of our approach is demonstrated with three molecular complexes. For two of these complexes, for which both the complex and the free protein structures have been solved, NMR titration data were available. Mutagenesis data were used in the last example. In all cases, the best structures generated by HADDOCK, that is, the structures with the lowest intermolecular energies, were the closest to the published structure of the respective complexes (within 2.0 A backbone RMSD).

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Crossref · 10.1021/ja026939x

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  • Conventional approaches for predicting protein complex structures include a docking component, which is limited by force-field accuracy and completeness of conformational space sampling.

    “conventional approaches for predicting the structure of protein complexes include a docking component8–11, which is limited by force-field accuracy and the completeness of conformational space sampling.”

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Authors
Dominguez, C., Boelens, R., & Bonvin, A. M. J. J.
Affiliations
Utrecht University (NL)
Corresponding author
Bonvin, Alexandre M. J. J.
Venue
Journal of the American Chemical Society
Published
2003-01-21
Volume
125
Issue
7
Pages
1731-1737
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
OpenAlex
W2153983456
Cited by
3,187
References
24
Citations by year
2026: 155 · 2025: 220 · 2024: 208 · 2023: 195 · 2022: 182 · 2021: 191 · 2020: 192 · 2019: 162 · 2018: 150 · 2017: 155 · 2016: 139 · 2015: 143 · 2014: 136 · 2013: 158 · 2012: 132
FWCI
16.70
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of the American Chemical Society (publishedVersion)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Leicester Research Archive (University of Leicester) (submittedVersion)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Keywords
protein-protein docking, haddock, chemical shift perturbation, NMR titration, protein-protein complex, structure determination, intermolecular interaction energy
MeSH terms
Bacterial Proteins, Models, Chemical, Models, Molecular, Phosphoenolpyruvate Sugar Phosphotransferase System, Proteins, HIV Envelope Protein gp120, CD4 Antigens, Protein Structure, Quaternary, Escherichia coli Proteins

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