Skip to main content

Prediction of Protein Structure and Function by Using Bioinformatics

  • Protocol
Genomics Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 175))

Abstract

Proteins mediate virtually all biological processes. Understanding the mechanisms by which proteins function requires a knowledge of their three-dimensional (3D) structures. As a consequence of the genome and full-length cDNA sequencing projects, there are several orders of magnitude more protein sequences compared with experimentally determined protein structures. To bridge this information gap, there is a considerable impetus to predict accurately the structures of proteins from sequence information. Protein structure prediction using bioinformatics can involve sequence similarity searches, multiple sequence alignments, identification and characterization of domains, secondary structure prediction, solvent accessibility prediction, automatic protein-fold recognition, and constructing 3D protein structures to atomic detail (see Fig. 1). The bioinformatics techniques used in predicting protein structure depend on the outcome from the analysis outlined in Fig. 1 and Table 1.

Protein structure prediction flowchart highlighting the steps involved in constructing 3D structural models from protein sequences by using bioinformatics.

Table 1 Types of Protein Structure Prediction Projects a

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Keller, P. A., Henrick, K., McNeil, P., Moodie, S., and Barton, G. J. (1998) Deposition of macromolecular structures. Acta Crystallogr. 54, 1105–1108.

    CAS  Google Scholar 

  2. Bray, J. E., Todd, A. E., Pearl, F. M., Thornton, J. M., and Orengo, C. A. (2000) The CATH Dictionary of Homologous Superfamilies (DHS): a consensus approach for identifying distant structural homologues. Protein Eng. 13, 153–165.

    Article  PubMed  CAS  Google Scholar 

  3. Lo Conte, L., Ailey, B., Hubbard, T. J., Brenner, S. E., Murzin, A. G., and Chothia C. (2000) SCOP: a structural classification of proteins database. Nucleic Acids Res. 28, 257–259.

    Article  PubMed  Google Scholar 

  4. Cottage, A., Clark, M., Hawker, K., Umrania, Y., Wheller, D., Bishop, M., and Elgar, G. (1999) Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes. FEBS Lett. 443, 370–374.

    Article  PubMed  CAS  Google Scholar 

  5. Trends Guide to Bioinformatics. (1998) Trends Supplement. Elsevier Science.

    Google Scholar 

  6. Attwood, T. K. and Parry-Smith, D. J. (1999) Introduction to Bioinformatics. Cell and Molecular Biology in Action Series. Addison Wesley Longman, Harlow, Essex, UK.

    Google Scholar 

  7. Barton, G. (1996) Protein sequence alignment and database scanning, in Protein Structure prediction: A Practical Approach (Sternberg, M. J. E., ed.), IRL, Oxford University Press, Oxford, UK, pp. 31–63.

    Google Scholar 

  8. Bishop, M. J., ed. (1999) Genetics Databases, Academic Press, San Diego, CA.

    Google Scholar 

  9. Branden, C. and Tooze, J. (1998) Introduction to Protein Structure, 2nd ed., Garland, New York and London.

    Google Scholar 

  10. Sternberg, M. J. E., ed. (1996) Protein Structure Prediction: A Practical Approach. IRL, Oxford University Press, Oxford, UK.

    Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Sonnhammer, E. L., Eddy, S. R., Birney, E., Bateman, A., and Durbin, R. (1998) Pfam: multiple sequence alignments and HMM-profiles of protein domains. Nucleic Acids Res. 26, 320–322.

    Article  PubMed  CAS  Google Scholar 

  13. Bork, P., Doerks, T., Springer, T. A., and Snel, B. (1999). Domains in plexins: links to integrins and transcription factors. Trends Biochem Sci. 24, 261–263.

    Article  PubMed  CAS  Google Scholar 

  14. Butler, B. A. (1998) Sequence Analysis Using GCG, in Bioformatics. A practical Guide to the Analysis of Genes and Proteins. (Baxevanis, A. D. and Ouellette, B. F. F., eds.), John Wiley, New York, pp. 74–97.

    Google Scholar 

  15. Cuff, J. A., Clamp, M. E., and Barton, G. J. (1998) JPred: A consensus secondary structure prediction server. Bioinformatics 14, 892–893.

    Article  PubMed  CAS  Google Scholar 

  16. Jones, D. T., Taylor, W. R., and Thornton, J. M. (1992) A new approach to protein fold recognition. Nature 358, 86–89.

    Article  PubMed  CAS  Google Scholar 

  17. Edwards, Y. J. K. and Perkins, S. J. (1996) Assessment of protein fold predictions from sequence information—the predicted alpha/beta doubly wound fold of the von Willebrand factor type A domain is similar to its crystal-structure. J. Mol. Biol. 260, 277–285.

    Article  PubMed  CAS  Google Scholar 

  18. Guex, N., Diemand, A., and Peitsch, M. C. (1999) Protein modelling for all. Trends Biochem Sci. 24, 364–367.

    Article  PubMed  CAS  Google Scholar 

  19. Vriend, G. (1990) What If: A molecular modeling and drug design program. J. Mol. Graph. 8, 52–56.

    Article  PubMed  CAS  Google Scholar 

  20. Laskowski, R. A., Rullmann, J. A., MacArthur, M. W., Kaptein, R., and Thornton, J. M. (1996) AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J. Biomol. NMR 8, 477–486.

    Article  PubMed  CAS  Google Scholar 

  21. Mizugochi, K., Deane, C. M., Blundell, T. L., Johnson, M. S., and Overington, J. P. (1998) Joy: protein sequence-structure representation and analysis. Bioinformatics 14, 617–623.

    Article  Google Scholar 

  22. Benner, S. A., Cannarozzi, G., Gerloff, D., Turcotte, D., and Chelvanayagam, M. (1997) Bona fide predictions of protein structure using transparent analyses of multiple sequence alignments. Chem. Rev. 97, 2725–2843.

    Article  PubMed  CAS  Google Scholar 

  23. Johnson, M. S., Srinivasan, N., Sowdhamini, R., and Blundell, T. L. (1994) Knowledge-based protein modeling. Crit. Rev. Biochem. Mol. Biol. 29, 1–68.

    Article  PubMed  CAS  Google Scholar 

  24. Sippl, M. J., Lackner, P., Domingues, F. S., and Koppensteiner, W. A. (1999) An attempt to analyse progress in fold recognition from CASP1 to CASP3. Proteins, 37(3), 226–230.

    Article  Google Scholar 

  25. Brocklehurst, S. M. and Perham, R. N. (1993) Prediction of the three-dimensional structures of the biotinylated domain from yeast pyruvate carboxylase and of the lipoylated H-protein from the pea leaf glycine cleavage system: a new automated method for the prediction of protein tertiary structure. Protein Sci. 4, 626–639.

    Google Scholar 

  26. Sander, C. and Schneider, R. (1991) Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9, 56–68.

    Article  PubMed  CAS  Google Scholar 

  27. Kabsch, W. and Sander, C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 12, 2577–2637.

    Article  Google Scholar 

  28. Kraulis, P. J. (1991) MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946–950.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Edwards, Y.J.K., Cottage, A. (2001). Prediction of Protein Structure and Function by Using Bioinformatics. In: Starkey, M.P., Elaswarapu, R. (eds) Genomics Protocols. Methods in Molecular Biology™, vol 175. Humana Press. https://doi.org/10.1385/1-59259-235-X:341

Download citation

  • DOI: https://doi.org/10.1385/1-59259-235-X:341

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-774-8

  • Online ISBN: 978-1-59259-235-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics