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Computational Prediction of Domain Interactions

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Comparative Genomics

Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 396))

Summary

Conserved domains carry many of the functional features found in the proteins of an organism. This includes not only catalytic activity, substrate binding, and structural features but also molecular adapters, which mediate the physical interactions between proteins or proteins with other molecules. In addition, two conserved domains can be linked not by physical contact but by a common function like forming a binding pocket.

Although a wealth of experimental data has been collected and carefully curated for protein–protein interactions, as of today little useful data is available from major databases with respect to relations on the domain level. This lack of data makes computational prediction of domain–domain interactions a very important endeavor.

In this chapter, we discuss the available experimental data (iPfam) and describe some important approaches to the problem of identifying interacting and/or functionally linked domain pairs from different kinds of input data. Specifically, we will discuss phylogenetic profiling on the level of conserved protein domains on one hand and inference of domain-interactions from observed or predicted protein–protein interactions datasets on the other. We explore the predictive power of these predictions and point out the importance of deploying as many different methods as possible for the best results

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References

  1. Pawson, T. and Nash, P. (2003) Assembly of cell regulatory systems through protein interaction domains. Science 300, 445–452.

    Article  CAS  PubMed  Google Scholar 

  2. Letunic, I., Goodstadt, L., Dickens, N. J., et al. (2002) Recent improvements to the SMART domain-based sequence annotation resource. Nucleic Acids Res. 30, 242–244.

    Article  CAS  PubMed  Google Scholar 

  3. Henikoff, J. G., Henikoff, S., and Pietrokovski, S. (1999) New features of the Blocks Database servers. Nucleic Acids Res. 27, 226–228.

    Article  CAS  PubMed  Google Scholar 

  4. Bateman, A., Coin, L., Durbin, R., et al. (2004) The Pfam protein families database. Nucleic Acids Res. 32, D138–D141.

    Article  CAS  PubMed  Google Scholar 

  5. Mulder, N. J., Apweiler, R., Attwood T. K., et al. (2005) InterPro, progress and status in 2005. Nucleic Acids Res. 33, D201–D205.

    Article  CAS  PubMed  Google Scholar 

  6. Xenarios, I., Salwìnski, L., Duan, X. J., Higney, P., Kim, S. -M., and Eisenberg, D. (2002) DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res. 30, 303–305.

    Article  CAS  PubMed  Google Scholar 

  7. Bader, G. D., Betel, D., and Hogue, C. W. V. (2003) BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248–250.

    Article  CAS  PubMed  Google Scholar 

  8. Peri, S., Navarro, J. D., Kristiansen, T. Z., et al. (2004) Human protein reference database as a discovery resource for proteomics. Nucleic Acids Res. 32, D497–D501.

    Article  CAS  PubMed  Google Scholar 

  9. Pagel, P., Kovac, S., Oesterheld, M., et al. (2005) The MIPS mammalian protein-protein interaction database. Bioinformatics 21, 832–834.

    Article  CAS  PubMed  Google Scholar 

  10. von Mering, C., Jensen, L. J., Snel, B., et al. (2005) STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33, D433–D437.

    Article  Google Scholar 

  11. Berman, H. M., Westbrook, J., Feng, Z., et al. (2000) The Protein Data Bank. Nucleic Acids Res. 28, 235–242.

    Article  CAS  PubMed  Google Scholar 

  12. Finn, R. D., Marshall, M., and Bateman, A. (2005) iPfam: visualization of protein-protein interactions in PDB at domain and amino acid resolutions. Bioinformatics 21, 410–412.

    Article  CAS  PubMed  Google Scholar 

  13. Stein, A., Russell, R. B., and Aloy, P. (2005) 3did: interacting protein domains of known three-dimensional structure. Nucleic Acids Res. 33, D413–D417.

    Article  CAS  PubMed  Google Scholar 

  14. Riley, R., Lee, C., Sabatti, C., and Eisenberg, D. (2005) Inferring protein domain interactions from databases of interacting proteins. Genome Biol. 6, R89.

    Article  PubMed  Google Scholar 

  15. Deng, M., Mehta, S., Sun, F., and Chen, T. (2002) Inferring domain-domain interactions from protein-protein interactions. Genome Res. 12, 1540–1548.

    Article  CAS  PubMed  Google Scholar 

  16. Huang, C., Kanaan, S. P., Wuchty, S., Chen, D. Z., and Izaguirre, J. A. (2004) Predicting protein-protein interactions from protein domains using a set cover approach. Submitted manuscript.

    Google Scholar 

  17. Kim, W. K., Park, J., and Suh, J. K. (2002) Large scale statistical prediction of protein-protein interaction by potentially interacting domain (PID) pair. Genome Inform. Ser. Workshop Genome Inform. 13, 42–50.

    CAS  Google Scholar 

  18. Pagel, P., Wong, P., and Frishman, D. (2004) A domain interaction map based on phylogenetic profiling. J. Mol. Biol. 344, 1331–1346.

    Article  CAS  PubMed  Google Scholar 

  19. Pellegrini, M., Marcotte, E. M., Thompson, M. J., Eisenberg, D., and Yeates, T. O. (1999) Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc. Natl. Acad. Sci. USA 96, 4285–4288.

    Article  CAS  PubMed  Google Scholar 

  20. Riley, M. L., Schmidt, T., Wagner, C., Mewes, H. -W., and Frishman, D. (2005) The PEDANT genome database in 2005. Nucleic Acids Res. 33, D308–D310.

    Article  CAS  PubMed  Google Scholar 

  21. Sprinzak, E. and Margalit, H. (2001) Correlated sequence-signatures as markers of protein-protein interaction. J. Mol. Biol. 311, 681–692.

    Article  CAS  PubMed  Google Scholar 

  22. Pagel, P., Oesterheld, M., Stümpflen, V., and Frishman, D. (2006) The DIMA web resource: exploring the protein domain network. Bioinformatics 22, 997–998.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was funded by a grant from the German Federal Ministry of Education and Research (BMBF) within the BFAM framework (031U112C). We would like to thank Robert Riley for helpful technical explanations regarding his algorithm, Thorsten Schmidt for helpful discussions, and Lousie Riley for careful reading of the manuscript.

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Pagel, P., Strack, N., Oesterheld, M., Stümpflen, V., Frishman, D. (2007). Computational Prediction of Domain Interactions. In: Bergman, N.H. (eds) Comparative Genomics. Methods In Molecular Biology™, vol 396. Humana Press. https://doi.org/10.1007/978-1-59745-515-2_1

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  • DOI: https://doi.org/10.1007/978-1-59745-515-2_1

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-37-4

  • Online ISBN: 978-1-59745-515-2

  • eBook Packages: Springer Protocols

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