E0024

High-throughput Approaches in Protein Structure Determination. A. Joachimiak, Bioscience Division, Structural Biology Center and Midwest Center for Structural Genomics, Argonne National Laboratory, 9700 South Cass Ave., Argonne, IL 60439,USA.

Genome sequencing efforts generated a large number of fully sequenced genomes of organisms belonging to all three kingdoms of life, including human. Bioinformatic analysis identified thousands of ORFs in these genomes, that presumably code for putative proteins of unknown function. Since biochemical function is associated with 3D structure, determination structures of these proteins will provide important information. However, determination of structures of thousands of novel proteins represents a major challenge. In spite tremendous progress in the past 40 years the structural biology effort is lagging behind genome sequencing. The multi-step process, from gene to protein 3D structure, spans many disciplines including molecular biology, protein chemistry, analytical chemistry, crystallography and computer science and involves processes on a very different time and space scale. Approaches and methods used traditionally in protein crystallography are inadequate for such a large scale project. The Midwest Center for Structural Genomics has developed new technology and automated methods that lower the effort and cost of many steps in the protein structure determination process. These approaches when combined with data collection facilities at third generation synchrotrons, advanced software and computing resources resulted in significant acceleration of protein structure determination and overall reduction of cost. Details of integration of such process and its implementation will be discussed.

This work was supported by the U.S. Department of Energy, Office of Biological and Environmental Research, under Contract W-31-109-ENG-38