An integrated approach to structural genomics

Structural genomics aims at determining a set of protein structures that will represent all domain folds present in the biosphere. These structures can be used as the basis for the homology modelling of the majority of all remaining protein domains or, indeed, proteins. Structural genomics therefore promises to provide a comprehensive structural description of the protein universe. To achieve this, a broad scientific effort is required. The Berlin-based "Protein Structure Factory" (PSF) plans to contribute to this effort by setting up a local infrastructure for the low-cost, high-throughput analysis of soluble human proteins. In close collaboration with the German Human Genome Project (DHGP) protein-coding genes will be expressed in Escherichia coli or yeast. Affinity-tagged proteins will be purified semi-automatically for biophysical characterization and structure analysis by X-ray diffraction methods and NMR spectroscopy. In all steps of the structure analysis process, possibilities for automation, parallelization and standardization will be explored. Major new facilities that are created for the PSF include a robotic station for large-scale protein crystallization, an NMR center and an experimental station for protein crystallography at the synchrotron storage ring BESSY II in Berlin.