Prism: Protein-Protein Interaction Prediction by Structural Matching

  • Ozlem Keskin
  • Ruth Nussinov
  • Attila Gursoy
Part of the Methods in Molecular Biology book series (MIMB, volume 484)


Prism (protein interactions by structural matching) is a system that employs a novel prediction algorithm for protein-protein interactions. It adopts a bottom-up approach that combines structure and sequence conservation in protein interfaces. The algorithm seeks possible binary interactions between proteins through structure similarity and evolutionary conservation of known interfaces. It is composed of a database containing protein interface structures derived from the Protein Data Bank (PDB) and predicted protein-protein interactions. It also provides related information about the proteins and an interactive protein interface viewer. In the current version, 3799 structurally nonredundant interfaces are used to predict the interactions among 6170 proteins. A substantial number of interactions are verified in two publicly available interaction databases (DIP and BIND). As the verified interactions demonstrate the suitability of our approach, unverified ones may point to undiscovered interactions. Prism can be accessed through a user-friendly website ( and it will be updated regularly as new protein structures become available in the PDB. Users may browse through the nonredundant dataset of representative interfaces on which the prediction algorithm depends, retrieve the list of structures similar to these interfaces, or see the results of interaction predictions for a particular protein. Another service provided is the interactive prediction. This is done by running the algorithm for the user input structures.

Key Words

Protein interactions protein interaction prediction protein interfaces protein databases 


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  1. 1.
    Bogan, A. A. and Thorn, K. S. (1998) Anatomy of hot spots in protein interfaces. J. Mol. Biol. 280, 1–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Chakrabarti, P. and Janin, J. (2002) Dissecting protein-protein recognition sites. Proteins 47, 334–343.PubMedCrossRefGoogle Scholar
  3. 3.
    Jones, S. and Thornton, J. M. (1997) Analysis of protein-protein interaction sites using surface patches. J. Mol. Biol. 272, 121–132.PubMedCrossRefGoogle Scholar
  4. 4.
    Lo Conte, L., Chothia, C., and Janin, J. (1999) The atomic structure of protein-protein recognition sites. J. Mol. Biol. 285, 2177–2198.PubMedCrossRefGoogle Scholar
  5. 5.
    Keskin, O., Ma, B., Rogale, K., Gunasekaran, K., and Nussinov, R. (2005) Protein-protein interactions: organization, cooperativity and mapping in a bottom-up systems biology approach. Phys. Biol. 2, S24–S35.PubMedCrossRefGoogle Scholar
  6. 6.
    Glaser, F., Steinberg, D. M., Vakser, I. A., and Ben-Tal, N. (2001) Residue frequencies and pairing preferences at protein-protein interfaces. Proteins 43, 89–102.PubMedCrossRefGoogle Scholar
  7. 7.
    Ito, T., Tashiro, K., Muta, S., Ozawa, R., Chiba, T., Nishizawa, M., Yamamoto, K., Kuhara, S., and Sakaki, Y. (2000) Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. Proc. Natl. Acad. Sci. USA 97, 1143–1147.PubMedCrossRefGoogle Scholar
  8. 8.
    Jones, S. and Thornton, J. M. (1995) Protein-protein interactions: a review of protein dimer structures. Prog. Biophys. Mol. Biol. 63, 31–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Neuvirth, H., Raz, R., and Schreiber, G. (2004) ProMate: a structure based prediction program to identify the location of protein-protein binding sites. J. Mol. Biol. 338, 181–199.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhou, H. X. and Shan, Y. (2001) Prediction of protein interaction sites from sequence profile and residue neighbor list. Proteins 44, 336–343.PubMedCrossRefGoogle Scholar
  11. 11.
    Clackson, T. and Wells, J. A. (1995) A hot spot of binding energy in a hormone-receptor interface. Science 267, 383–386.PubMedCrossRefGoogle Scholar
  12. 12.
    DeLano, W. L. (2002) Unraveling hot spots in binding interfaces: progress and challenges. Curr. Opin. Struct. Biol. 12, 14–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Keskin, O., Ma, B., and Nussinov, R. (2005) Hot regions in protein-protein interactions: the organization and contribution of structurally conserved hot spot residues. J. Mol. Biol. 345, 1281–1294.PubMedCrossRefGoogle Scholar
  14. 14.
    Ma, B., Wolfson, H. J., and Nussinov, R. (2001) Protein functional epitopes: hot spots, dynamics and combinatorial libraries. Curr. Opin. Struct. Biol. 11, 364–369.PubMedCrossRefGoogle Scholar
  15. 15.
    Uetz, P., Giot, L., Cagney, G., Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi-Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., and Rothberg, J. M. (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., Mitchell, T., Miller, P., Dean, R. A., Gerstein, M., and Snyder, M. (2001) Global analysis of protein activities using proteome chips. Science 293, 2101–2105.PubMedCrossRefGoogle Scholar
  17. 17.
    Kortemme, T. and Baker, D. (2004) Computational design of protein-protein interactions. Curr. Opin. Chem. Biol. 8, 91–97.PubMedCrossRefGoogle Scholar
  18. 18.
    Keskin, O., Tsai, C. J., Wolfson, H., and Nussinov, R. (2004) A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications. Protein Sci. 13, 1043–1055.PubMedCrossRefGoogle Scholar
  19. 19.
    Winter, C., Henschel, A., Kim, W. K., and Schroeder, M. (2006) SCOPPI: a structural classification of protein-protein interfaces. Nucleic Acids Res. 34, D310–314.PubMedCrossRefGoogle Scholar
  20. 20.
    Aytuna, A. S., Gursoy, A., and Keskin, O. (2005) Prediction of protein-protein interactions by combining structure and sequence conservation in protein interfaces. Bioinformatics 21, 2850–2855.PubMedCrossRefGoogle Scholar
  21. 21.
    Murakami, Y. and Jones, S. (2006) SHARP2: protein-protein interaction predictions using patch analysis. Bioinformatics 22, 1794–1795.PubMedCrossRefGoogle Scholar
  22. 22.
    Aloy, P., Bottcher, B., Ceulemans, H., Leutwein, C., Mellwig, C., Fischer, S., Gavin, A. C., Bork, P., Superti-Furga, G., Serrano, L., and Russell, R. B. (2004) Structure-based assembly of protein complexes in yeast. Science 303, 2026–2029.PubMedCrossRefGoogle Scholar
  23. 23.
    Ogmen, U., Keskin, O., Aytuna, A. S., Nussinov, R., and Gursoy, A. (2005) PRISM: protein interactions by structural matching. Nucleic Acids Res. 33, W331–336.PubMedCrossRefGoogle Scholar
  24. 24.
    Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., and Bourne, P. E. (2000) The Protein Data Bank. Nucleic Acids Res. 28, 235–242.PubMedCrossRefGoogle Scholar
  25. 25.
    Nussinov, R. and Wolfson, H. J. (1991) Efficient detection of three-dimensional structural motifs in biological macromolecules by computer vision techniques. Proc. Natl. Acad. Sci. USA 88, 10495–10499.PubMedCrossRefGoogle Scholar
  26. 26.
    Ma, B., Elkayam, T., Wolfson, H., and Nussinov, R. (2003) Protein-protein interactions: structurally conserved residues distinguish between binding sites and exposed protein surfaces. Proc. Natl. Acad. Sci. USA 100, 5772–5777.PubMedCrossRefGoogle Scholar
  27. 27.
    Shatsky, M., Nussinov, R., and Wolfson, H. J. (2004) A method for simultaneous alignment of multiple protein structures. Proteins 56, 143–156.PubMedCrossRefGoogle Scholar
  28. 28.
    Hubbard, S. J. and Thornton, J. M. (1993) “NACCESS,” computer program. Department of Biochemistry and Molecular Biology, University College, London.Google Scholar
  29. 29.
    Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D. J. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402.PubMedCrossRefGoogle Scholar
  30. 30.
    Xenarios, I., Salwinski, 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.PubMedCrossRefGoogle Scholar
  31. 31.
    Bader, G. D., Betel, D., and Hogue C. W. (2003) BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248–250.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, Totowa, NJ 2008

Authors and Affiliations

  • Ozlem Keskin
    • 1
  • Ruth Nussinov
    • 2
    • 3
  • Attila Gursoy
    • 1
  1. 1.Center for Computational Biology and Bioinformatics and College of EngineeringKoc UniversityIstanbulTurkey
  2. 2.Basic Research ProgramSAIC-Frederick, Inc. Center for Cancer Research Nanobiology Program NCI-FrederickFrederickUSA
  3. 3.Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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