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Structural bioinformatics: from protein structure to function

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Book cover Evolving Methods for Macromolecular Crystallography

Part of the book series: NATO Science Series ((NAII,volume 245))

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A major problem faced by structural biology today is the issue of function prediction. With the success of the various Structural genomics initiatives and advances in crystallography, proteomics, and other experimental techniques, there has been an explosion of new protein structures being deposited in the databases. In many cases, however, these proteins have little or no functional annotation. Sequence-based approaches still remain the most effective way to assign function based on homology, but in cases of extreme divergence and analogous proteins these methods can fail. In order to identify these types of relationships, a number of structure-based approaches have been developed, such as the MSDmotif service. No single method is successful in all cases and a more prudent approach involves the utilization of data from a wide range of resources. One such approach is the ProFunc server, developed to help researchers narrow down the number of functional possibilities for experimental validation.

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References

  1. 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 Research, 28: 235–242.

    Article  Google Scholar 

  2. Golovin, A., Dimitropoulos, D., Oldfield, T., Rachedi A., and Henrick, K. (2005) MSDsite: A Database Search and Retrieval System for the Analysis and Viewing of Bound Ligands and Active Sites. Proteins: Structure, Function, and Bioinformatics, 58(1): 190–199.

    Article  Google Scholar 

  3. Golovin, A. (2004) MSDmotif: a database search and retrieval system for the analysis and viewing of protein structure motifs. The eCheminfo 2005 Conference “Webservices” 13 June.

    Google Scholar 

  4. Hulo, N., Sigrist, C.J.A., Le Saux, V., Langendijk-Genevaux, P.S., Bordoli, L., Gattiker, A., De Castro, E., Bucher, P., and Bairoch, A. (2004) Recent improvements to the PROSITE database. Nucleic Acids Research, 32: D134–D137.

    Article  Google Scholar 

  5. Laskowski, R.A., Watson, J.D., and Thornton, J.M. (2005) ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Research, 33: W89–W93.

    Article  Google Scholar 

  6. Karplus, K., Barrett, C., and Hughey, R. (1998) Hidden Markov models for detecting remote protein homologies. Bioinformatics, 14: 846–856.

    Article  Google Scholar 

  7. 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 Research, 25: 3389–3402.

    Article  Google Scholar 

  8. Pearson, W.R. (1998) Empirical statistical estimates for sequence similarity scores. Journal of molecular biology, 276: 71–84.

    Article  Google Scholar 

  9. Apweiler, R., Bairoch, A., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M. Martin, M.J., Natale, D.A., O’Donovan, C., Redaschi, N., and Yeh, L.S. (2004) UniProt: the Universal Protein Knowledgebase. Nucleic Acids Research, 32: D115–D119.

    Article  Google Scholar 

  10. Madera, M., Vogel, C., Kummerfeld, S.K., Chothia, C., and Gough, J.—(2004) The SUPERFAMILY database in 2004: additions and improvements. Nucleic Acids Research, 32: D235–D239.

    Article  Google Scholar 

  11. Whisstock, J.C., and Lesk, A.M. (2003) Prediction of protein function from protein sequence and structure. Quarterly Reviews of Biophysics, 36(3): 307–340.

    Article  Google Scholar 

  12. Mulder, N.J., Apweiler, R., Attwood, T.K., Bairoch, A., Barrell, D., Bateman, A., Binns, D., Biswas, M., Bradley, P., Bork, P., et—al. (2003) The InterPro Database, 2003 brings increased coverage and new features. Nucleic Acids Research, 31: 315–318.

    Article  Google Scholar 

  13. Bateman, A., Birney, E., Cerruti, L., Durbin, R., Etwiller, L., Eddy, S.R., Griffiths-Jones, S., Howe, K.L., Marshall, M., and Sonnhammer, E.L. (2002) The Pfam protein families database. Nucleic Acids Research, 30(1): 276–280.

    Article  Google Scholar 

  14. Higgins, D., Thompson, J., Gibson, T., Thompson, J.D., Higgins, D.G., and Gibson, T.J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research, 22: 4673–4680.

    Article  Google Scholar 

  15. Valdar, W.S.J., and Thornton, J.M. (2001) Conservation helps to identify biologically relevant crystal contacts. Journal of Molecular Biology, 313: 399–416.

    Article  Google Scholar 

  16. George, R.A., Spriggs, R.G., Bartlett, G.J., Gutteridge, A., MacArthur, M.W., Porter, C.T., Al-Lazikani, B., Thornton, J.M., and Swindells, M.B. (2005) Effective function annotation through residue conservation. Proceedings of the National Academy of Sciences of the USA, 102: 12299–12304.

    Article  ADS  Google Scholar 

  17. Ponstingl, H., Kabir, T., and Thornton, J.—M. (2002) Automatic inference of protein quaternary structure from crystals. Journal of Applied Crystallography, 36: 1116–1122.

    Article  Google Scholar 

  18. Holm, L., and Sander, C. (1995) Dali: a network tool for protein structure comparison. Trends in Biochemical Sciences, 20: 478–480.

    Article  Google Scholar 

  19. Shindyalov, I.N., and Bourne, P.E. (1998) Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Engineering, 11: 739–747.

    Article  Google Scholar 

  20. Madej, T., Gibrat, J.F., and Bryant, S.H. (1995) Threading a database of protein cores. Proteins, 23(3): 356–369.

    Article  Google Scholar 

  21. Krissinel, E., and Henrick, K. (2004) Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallographica, D60: 2256–2268.

    Google Scholar 

  22. Ferrer-Costa, C., Shanahan, H.P., Jones, S., and Thornton, J.M. (2005) HTHquery: a method for detecting DNA-binding proteins with a helix-turn-helix structural motif. Bioinformatics, 21: 3679–3680.

    Article  Google Scholar 

  23. Laskowski, R.A. (1995) SURFNET: a program for visualizing molecular surfaces, cavities and intermolecular interactions. Journal of Molecular Graphics, 13: 323–330.

    Article  Google Scholar 

  24. Watson, J.D., and Milner-White, E.J. (2002) A novel main-chain anion-binding site in proteins: the nest. A particular combination of phi, psi values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions. Journal of Molecular Biology, 315(2): 171–182.

    Article  Google Scholar 

  25. Watson, J.D., and Milner-White, E.J. (2002) The conformations of polypeptide chains where the main-chain parts of successive residues are enantiomeric. Their occurrence in cation and anion-binding regions of proteins. Journal of Molecular Biology, 315(2): 183–191.

    Article  Google Scholar 

  26. Porter, C.T., Bartlett, G.J., and Thornton, J.M. (2004) The Catalytic Site Atlas: a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic Acids Research, 32: D129–D133.

    Article  Google Scholar 

  27. Barker, J.A., and Thornton, J.M. (2003) An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis. Bioinformatics, 19: 1644–1649.

    Article  Google Scholar 

  28. Torrance, J.W., Bartlett, G.J., Porter, C. T., and Thornton, J.M. (2005) Using a library of structural templates to recognise catalytic sites and explore their evolution in homologous families. Journal of Molecular Biology, 347: 565–581.

    Article  Google Scholar 

  29. Laskowski, R.A., Watson, J.D., and Thornton, J.M. (2005) Protein function prediction using local 3D templates. Journal of Molecular Biology, 351: 614–626.

    Article  Google Scholar 

  30. Sanishvili, R., Yakunin, A.F., Laskowski, R.A., Skarina, T., Evdokimova, E., Doherty-Kirby, A., Lajoie, G.A., Thornton, J.M., Arrowsmith, C.H., Savchenko, A., Joachimiak, A., and Edwards, A.M. (2003) Integrating structure, bioinformatics, and enzymology to discover function–BioH, a new carboxylesterase from Escherichia coli. The Journal of Biological Chemistry, 278: 26039–26045.

    Article  Google Scholar 

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Edwards, A.M. et al. (2007). Structural bioinformatics: from protein structure to function. In: Read, R.J., Sussman, J.L. (eds) Evolving Methods for Macromolecular Crystallography. NATO Science Series, vol 245. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6316-9_14

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