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The ClusPro web server for protein–protein docking

Nature Protocols volume 12, pages 255–278 (2017)Cite this article

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Abstract

The ClusPro server (https://cluspro.org) is a widely used tool for protein–protein docking. The server provides a simple home page for basic use, requiring only two files in Protein Data Bank (PDB) format. However, ClusPro also offers a number of advanced options to modify the search; these include the removal of unstructured protein regions, application of attraction or repulsion, accounting for pairwise distance restraints, construction of homo-multimers, consideration of small-angle X-ray scattering (SAXS) data, and location of heparin-binding sites. Six different energy functions can be used, depending on the type of protein. Docking with each energy parameter set results in ten models defined by centers of highly populated clusters of low-energy docked structures. This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results. Although the server is heavily used, runs are generally completed in <4 h.

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Figure 1: Outline of the ClusPro algorithm.
Figure 2: Home screen of the ClusPro server.
Figure 3: Screen capture of the restraint file generator web tool used to prepare a JSON file.
Figure 4: Screen capture of the ClusPro Status page.
Figure 5: Screen capture of the ClusPro Results page for docking of the soybean trypsin inhibitor (ligand) to the porcine trypsin (receptor).
Figure 6: Screen capture of the ClusPro Results page showing model scores for the balanced coefficient set when docking the soybean trypsin inhibitor to porcine trypsin.
Figure 7: Visualization by PyMol of the structure at the center of the most populated cluster in docking the soybean trypsin inhibitor (ligand) to porcine trypsin (receptor).
Figure 8: Screen capture showing exploration of the results of running ClusPro in 'Others Mode'.
Figure 9: Screen capture of the PyMOL visualization of the results of running ClusPro in Antibody Mode.
Figure 10: Best models from docking the signal-transducing protein HPr (PDB ID 1POH) to the glucose-specific phosphocarrier protein E2A (PDB ID 1F3G) without and with restraints.
Figure 11: Docking of the E. coli PliG lysozyme inhibitor to the salmon goose-type lysozyme using SAXS data as restraints.
Figure 12: Constructing the dimer of the sugar aminotransferase AtmS13 from Actinomadura melliaura by homology modeling and multimer docking.
Figure 13: Docking of the heparin tetramer probe to the ligand-free structure of the basic fibroblast growth factor.

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Acknowledgements

This investigation was supported by grants R35 GM118078 and R01 GM061867 from the National Institute of General Medical Sciences to S.V., and grants DBI 1147082, DBI 1458509, and AF 1527292 from the National Science Foundation to S.V. and D.K.

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Authors and Affiliations

  1. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, USA

    Dima Kozakov & Dzmitry Padhorny

  2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA

    Dima Kozakov, Bing Xia, Kathryn A Porter, Christine Yueh, Dmitri Beglov & Sandor Vajda

  3. Laufer Center for Physical and Quantitative Biology, Stony Brook University, New York, USA

    Dima Kozakov

  4. Acpharis Inc., Holliston, Massachusetts, USA

    David R Hall

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  1. Dima Kozakov
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Contributions

D.K., D.R.H., B.X., and D.B. developed the server; D.K., D.R.H., D.P., B.X., and K.A.P. performed experiments; S.V., K.A.P., D.R.H., and C.Y. prepared the manuscript.

Corresponding authors

Correspondence to Dima Kozakov or Sandor Vajda.

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Competing interests

The PIPER docking program, used in the ClusPro server, has been licensed by Boston University to Acpharis Inc., and to Schrodinger LLC. The companies sublicense the program for commercial use. However, the ClusPro server is free for academic and governmental research.

Supplementary information

Supplementary Table 1

Performance of ClusPro on Docking Benchmark 4.0. (PDF 99 kb)

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Kozakov, D., Hall, D., Xia, B. et al. The ClusPro web server for protein–protein docking. Nat Protoc 12, 255–278 (2017). https://doi.org/10.1038/nprot.2016.169

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