Protein–Protein Docking: Overview and Performance Analysis

  • Kevin Wiehe
  • Matthew W. Peterson
  • Brian Pierce
  • Julian Mintseris
  • Zhiping Weng
Part of the Methods in Molecular Biology™ book series (MIMB, volume 413)


Protein–protein docking is the computational prediction of protein complex structure given the individually solved component protein structures. It is an important means for understanding the physicochemical forces that underlie macromolecular interactions and a valuable tool for modeling protein complex structures. Here, we report an overview of protein–protein docking with specific emphasis on our Fast Fourier Transform-based rigid-body docking program ZDOCK, which is consistently rated as one of the most accurate docking programs in the Critical Assessment of Predicted Interactions (CAPRI), a series of community-wide blind tests. We also investigate ZDOCK’s performance on a non-redundant protein complex benchmark. Finally, we perform regression analysis to better understand the strengths and weaknesses of ZDOCK and to suggest areas of future development for protein-docking algorithms in general.


Protein–protein docking ZDOCK RDOCK Fast Fourier Transform benchmark CAPRI shape complementarity electrostatics desolvation energy regression analysis 



We are grateful to the Scientific Computing Facilities at Boston University and the Advanced Biomedical Computing Center at NCI, NIH for support in computing. This work was funded by NSF grants DBI-0133834 and DBI-0116574.


  1. 1.
    Betts, M.J. and M.J. Sternberg. An analysis of conformational changes on protein-protein association: implications for predictive docking. Protein Eng, 1999, 12(4): p. 271–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Katchalski-Katzir, E., et al. Molecular surface recognition: determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci USA, 1992, 89(6): p. 2195–9.Google Scholar
  3. 3.
    Chen, R. and Z. Weng. Docking unbound proteins using shape complementarity, desolvation, and electrostatics. Proteins, 2002, 47(3): p. 281–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Gabb, H.A., R.M. Jackson, and M.J. Sternberg. Modelling protein docking using shape complementarity, electrostatics and biochemical information. J Mol Biol, 1997, 272(1): p. 106–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Vakser, I.A. Protein docking for low-resolution structures. Protein Eng, 1995, 8(4): p. 371–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Ritchie, D.W. and G.J. Kemp. Protein docking using spherical polar Fourier correlations. Proteins, 2000, 39(2): p. 178–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Palma, P.N., et al. BiGGER: a new (soft) docking algorithm for predicting protein interactions. Proteins, 2000, 39(4): p. 372–84.CrossRefPubMedGoogle Scholar
  8. 8.
    Abagyan, R., M. Totrov, and D. Kuznetsov. ICM – a new method for protein modeling and design – applications to docking and structure prediction from the distorted native conformation. J Comput Chem, 1994, 15(5): p. 488–506.CrossRefGoogle Scholar
  9. 9.
    Gray, J.J., et al. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol, 2003, 331(1): p. 281–99.CrossRefPubMedGoogle Scholar
  10. 10.
    Gardiner, E.J., P. Willett, and P.J. Artymiuk. Protein docking using a genetic algorithm. Proteins, 2001, 44(1): p. 44–56.CrossRefPubMedGoogle Scholar
  11. 11.
    Fischer, D., et al. A geometry-based suite of molecular docking processes. J Mol Biol, 1995, 248(2): p. 459–77.PubMedGoogle Scholar
  12. 12.
    Morris, G.M., et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem, 1998, 19(14): p. 1639–62.CrossRefGoogle Scholar
  13. 13.
    Comeau, S.R., et al. ClusPro: an automated docking and discrimination method for the prediction of protein complexes. Bioinformatics, 2004, 20(1): p. 45–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Kuntz, I.D., et al. A geometric approach to macromolecule-ligand interactions. J Mol Biol, 1982, 161(2): p. 269–88.CrossRefPubMedGoogle Scholar
  15. 15.
    Mandell, J.G., et al. Protein docking using continuum electrostatics and geometric fit. Protein Eng, 2001, 14(2): p. 105–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Dominguez, C., R. Boelens, and A.M. Bonvin. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J Am Chem Soc, 2003, 125(7): p. 1731–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Schneidman-Duhovny, D., et al. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res, 2005, 33(Web Server issue): p. W363–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Chen, R., L. Li, and Z. Weng. ZDOCK: an initial-stage protein-docking algorithm. Proteins, 2003, 52(1): p. 80–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Janin, J., et al. CAPRI: a critical assessment of predicted interactions. Proteins, 2003, 52(1): p. 2–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Moult, J., et al. Critical assessment of methods of protein structure prediction (CASP) –round 6. Proteins, 2005, 61 Suppl 7: p. 3–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Vajda, S. Classification of protein complexes based on docking difficulty. Proteins, 2005, 60(2): p. 176–80.CrossRefPubMedGoogle Scholar
  22. 22.
    Delano, W.L. The PyMOL Molecular Graphics System, 2002.Google Scholar
  23. 23.
    Chen, R., et al. A protein-protein docking benchmark. Proteins, 2003, 52(1): p. 88–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Kozakov, D., et al. Optimal clustering for detecting near-native conformations in protein docking. Biophys J, 2005, 89(2): p. 867–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Duan, Y., B.V. Reddy, and Y.N. Kaznessis. Physicochemical and residue conservation calculations to improve the ranking of protein-protein docking solutions. Protein Sci, 2005, 14(2): p. 316–28.CrossRefPubMedGoogle Scholar
  26. 26.
    Tovchigrechko, A. and I.A. Vakser. Development and testing of an automated approach to protein docking. Proteins, 2005, 60(2): p. 296–301.CrossRefPubMedGoogle Scholar
  27. 27.
    Mintseris, J., et al. Protein-Protein Docking Benchmark 2.0: an update. Proteins, 2005, 60(2): p. 214–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Murzin, A.G., et al. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol, 1995, 247(4): p. 536–40.PubMedGoogle Scholar
  29. 29.
    Berman, H.M., et al. The Protein Data Bank. Nucleic Acids Res, 2000, 28(1): p. 235–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang, C., et al. Determination of atomic desolvation energies from the structures of crystallized proteins. J Mol Biol, 1997, 267(3): p. 707–26.CrossRefPubMedGoogle Scholar
  31. 31.
    Chen, R. and Z. Weng. A novel shape complementarity scoring function for protein-protein docking. Proteins, 2003, 51(3): p. 397–408.CrossRefPubMedGoogle Scholar
  32. 32.
    Brooks, B.R., et al. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem, 1983, 4: p. 187–217.CrossRefGoogle Scholar
  33. 33.
    Li, L., R. Chen, and Z. Weng. RDOCK: refinement of rigid-body protein docking predictions. Proteins, 2003, 53(3): p. 693–707.CrossRefPubMedGoogle Scholar
  34. 34.
    Pierce, B., W. Tong, and Z. Weng. M-ZDOCK: a grid-based approach for Cn symmetric multimer docking. Bioinformatics, 2005, 21(8): p. 1472–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Laskowski, R.A. SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. J Mol Graph Model, 1995, 13(5): p. 323–30, 307–8.Google Scholar
  36. 36.
    Mintseris, J. and Z. Weng. Optimizing protein representations with information theory. Genome Inform Ser Workshop Genome Inform, 2004, 15(1): p. 160–9.Google Scholar
  37. 37.
    Dunbrack, R.L., Jr. and M. Karplus. Backbone-dependent rotamer library for proteins. Application to side-chain prediction. J Mol Biol, 1993, 230(2): p. 543–74.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc 2008

Authors and Affiliations

  • Kevin Wiehe
  • Matthew W. Peterson
  • Brian Pierce
  • Julian Mintseris
  • Zhiping Weng

There are no affiliations available

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