W0448

Structure Determination as a First Step in Function Analysis of Hypothetical Proteins. Adam Godzik, Yuzhen Ye, Iddo Friedberg, Lukasz Jaroszewski, Bioinformatics, The Burnham Inst., 10901 N. Torrey Pines Rd., La Jolla, CA 92037 USA.

Until recently, structure determination was usually the last step in a long process of experimental characterization of a protein, so a crystallographer could draw on a large body of information when interpreting the structure. With the advent of genome sequencing project and improving techniques for cloning, we increasingly solve structures of novel, completely uncharacterized proteins - sometimes just because “they are there”. In such cases, structure is often the first experimental information we have about a otherwise unknown protein. What can we do to explore the structure for functional hints?

In this talk I’ll survey a number of existing and emerging approaches to address this problem. Generally they can be described as extended structure comparison to other, better characterized proteins, often focusing not only on overall topology, but small, function related structural features - charged or hydrophobic patches on the surface, presence of specific loops, local environments etc. Many such methods can be enhanced by additional sequence and genomic analysis tools - distant homology recognition, genomic context analysis and multiple alignment analysis.