An integrated approach to structural genomics

Structural genomics aims at determining a set of protein structures that wi ll represent all domain folds present in the biosphere. These structures ca n be used as the basis for the homology modelling of the majority of all re maining 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 Berli n-based "Protein Structure Factory" (PSF) plans to contribute to this effor t by setting up a local infrastructure for the low-cost, high-throughput an alysis of soluble human proteins. In close collaboration with the German Hu man Genome Project (DHGP) protein-coding genes will be expressed in Escheri chia coli or yeast. Affinity-tagged proteins will be purified semi-automati cally for biophysical characterization and structure analysis by X-ray diff raction methods and NMR spectroscopy. In all steps of the structure analysi s process, possibilities for automation, parallelization and standardizatio n will be explored. Major new facilities that are created for the PSF inclu de 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. (C) 2000 Elsevier Science Ltd. All rights reserved.