Home > CSSS Seminars > Kenji Mizuguchi   Kenji Mizuguchi Department of Biochemistry, University of Cambridge Cambridge, UK Homology Recognition Using FUGUE: from Sequence to Structure and Function Completed genomes of various organisms offer a rich source of information about proteins involved in important biological processes. The lack of obvious sequence similarity, as in many cases, does not exclude the possibility that they are evolutionarily related (i.e., homologous) to other proteins of known three-dimensional (3D) structure and function. In fact, such a link, once established, will not only increase our knowledge of the system but also can even lead to the identification of novel drug targets. We have developed FUGUE (http://www-cryst.bioc.cam.ac.uk/~fugue/); [1]), a software program that can associate genome sequences with proteins of known structure. By utilizing the information about the structural environment of each amino acid residue, capturing it in environment-specific substitution scores, a more accurate estimation of evolution can be obtained than conventional sequence comparison methods. The software has been proven as one of the more successful structure prediction methods in community-wide exercises such as CASP (http://predictioncenter.llnl.gov/casp5/) and LiveBench (http://bioinfo.pl/livebench/). Identifying distant homologues can provide novel insights into the functional mechanisms for enzyme families [2]. Bridging two transporter proteins shed light into the evolution of the bacterial import systems [3]. This type of approach can be also useful for verifying gene prediction [4] and even experimental structures. With various types of large-scale data (such as expression and protein-protein interaction profiles) now available, a major challenge in bioinformatics is to integrate these data and provide a better picture of biological systems. One such attempt is an integrated database for Drosophila and Anopheles genomics (http://www.flymine.org), where we plan to map known mutations in Drosophila to predicted 3D structures. References: [1] Shi, J., Blundell, T.L. and Mizuguchi, K. (2001) J Mol Biol 310, 243-57. [2] Shirai, H., Blundell, T.L. and Mizuguchi, K. (2001) Trends Biochem Sci 26, 465-8. [3] Witty, M., Sanz, C., Shah, A., Grossmann, J.G., Mizuguchi, K., Perham, R.N. and Luisi, B. (2002) Embo J 21, 4207-18. [4] Parker, J.S., Mizuguchi, K. and Gay, N.J. (2001) Proteins 45, 71-80.
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