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Reply to ‘Defining distance restraints in HADDOCK’

Nature Protocols volume 13, pages 1503–1505 (2018)Cite this article

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Orbán-Németh et al. reply — In our recently published protocol in Nature Protocols, we provide instructions on how to use cross-linking mass spectrometry (XL-MS) data to predict structural models of proteins and their complexes1. In our protocol, we describe the use of several software programs, including HADDOCK2, which is used for protein–protein docking. We are grateful to the HADDOCK developers for carefully reading our recent publication and for identifying and pointing out that Step 21 of our procedure describes an erroneous syntax for distance restraint definition3, which we used for docking via their HADDOCK web portal. We agree with the distance restraint definition described by Bonvin et al.3 and we encourage the use of our protocol with the correct cross-linking restraint definition as defined by the developers of the method4,5,6.

assign (resid <residue number> and segid <1st molecule chain>) (resid <residue number> and segid <2nd molecule chain>) <target distance> <lower distance margin> <higher distance margin>

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Fig. 1: Crystal structure of the HOP2–MND1 heterodimer and selected best protein complex models obtained after the final HADDOCK docking step.

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Acknowledgements

Research was funded by the Austrian Science Fund (SFB F34: Z.O.-N., E.R., T.S.). We thank IMP and IMBA for general funding. Molecular graphics and analyses were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311). Images in Chimera were created using Persistence of Vision Raytracer (version 3.6), Persistence of Vision, Pty. Ltd. (2004), retrieved from http://www.povray.org/download/.

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Authors and Affiliations

  1. Mass Spectrometry and Protein Chemistry, Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria

    Zsuzsanna Orbán-Németh, Rebecca Beveridge, Evelyn Rampler, Thomas Stranzl, Otto Hudecz, Johannes Doblmann & Karl Mechtler

  2. Mass Spectrometry and Protein Chemistry, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria

    Zsuzsanna Orbán-Németh, Rebecca Beveridge, Evelyn Rampler, Thomas Stranzl, Otto Hudecz, Johannes Doblmann & Karl Mechtler

  3. Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

    David M. Hollenstein

  4. Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria

    Evelyn Rampler

  5. Department of Chromosome Biology, Max F. Perutz Laboratories, University of Viehnna, Vienna, Austria

    Peter Schlögelhofer

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  1. Zsuzsanna Orbán-Németh
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Supplementary Figure 1 Crystal structure of the PPP2R1A–PPP2CA complex and selected best protein complex models obtained after the final HADDOCK docking step.

(a) Selected model after re-calculation using the correct distance restraints between residues. This model displayed the best HADDOCK score among the models satisfying all three cross-links and a high XL score. (b) Selected model after re-calculation using the correct distance restraints between specific atoms. This model displayed the best HADDOCK score and XL score. (c) Selected model as presented in our protocol, calculated using the erroneously short distance restraints. (d) Crystal structure of the PPP2R1A–PPP2CA complex: PDB entry 2IAE. (a-d) Cross-links are shown in green. PPP2R1A and PPP2CA are colored light and dark, respectively

Supplementary Figure 2 Crystal structure of the plectin-calmodulin complex and selected best protein complex models obtained after the final HADDOCK docking step.

(a) Selected model after re-calculation using the correct distance restraints between residues. This model displayed the best HADDOCK score and XL score. (b) Selected model after re-calculation using the correct distance restraints between specific atoms. This model displayed the best combination of HADDOCK score and XL score. (c) Selected model as presented in our protocol, calculated using the erroneously short distance restraints. (d) Crystal structure of the plectin-calmodulin complex: PDB ID 4Q57. (a-d) The calmodulin chain is colored red

Supplementary Figure 3 Inter-protein cross-links mapped onto the predicted best model of the plectin-calmodulin complex derived from re-calculation using the corrected distance restraints between residues for HADDOCK.

(a) Compatible and (b) incompatible cross-links are mapped onto the selected model and are colored green and orange, respectively. (a and b) The calmodulin chain is colored red, the plectin chain blue, calcium is shown as green spheres. E14 of calmodulin and R40 of plectin, the residues involved in formation of a salt bridge, are shown as sticks and are colored green and yellow, respectively

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Orbán-Németh, Z., Beveridge, R., Hollenstein, D.M. et al. Reply to ‘Defining distance restraints in HADDOCK’. Nat Protoc 13, 1503–1505 (2018). https://doi.org/10.1038/s41596-018-0018-5

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