Synchrotron radiation (SR) is an extremely bright and tunable x-ray source that enables forefront research in structural molecular biology (8MB). A """"""""Synchrotron Structural Biology Resource"""""""" is supported at the Stanford Synchrotron Radiation Laboratory (SSRL) by the NIH and DOE to develop technologies in macromolecular crystallography, x-ray absorption spectroscopy and small angle x-ray scattering/diffraction and to disseminate these methodologies for use in the biomedical research community. This proposal is for the continued funding, operation and further development of this Resource. New initiatives will capitalize on the remarkable enhancement in SR performance resulting from the completed upgrade of the SSRL storage ring to a 3d'generation source (SPEARS). Proposed also is a new focus on SMB applications of ultrashort pulse, ultrabright x-rays from what will be the world's first x-ray free-electron laser (LCLS) being pioneered at SLAC. A principal aim is to optimize experimental facilities, detectors, software and computer capacity on the 9+ SMB beam lines at SSRL (and a 10th in construction) to take full advantage of the increased brightness provided by SPEARS. This will enable the Resource to advance the scientific forefront with new initiatives built upon novel instrumentation (especially advanced detectors), innovative software and automated/high-throughput systems for: studying high resolution structures of large, complex macromolecules, including molecular machines;imaging the spacial distribution and chemical nature of elements in non-crystalline biological materials;investigating fundamental questions in biophysics such as protein and RNA folding;developing and improving methods for imaging non-crystalline biological materials at near atomic resolution;and studying very fast time-resolved structural changes in chemical and biological systems with ultrafast absorption and scattering techniques. These scientific advancements will be facilitated by parallel developments in software to provide expanded capabilities for instrument and detector control, remote data collection and real-time data analysis. Strong collaborative research programs involving a large number of outside scientists will drive and support core technological developments. Relevance is to a number of important biological problems including the structure of enzymes, metalloproteins, membranebound proteins and immunoglobulins;the active site structure of metalloproteins involved in oxygen metabolism, nitrogen fixation, and photosynthesis;and how these structures change in different states or evolve in time as reactions or events like protein folding or conformational changes occur. Such information is more broadly important to the health-related areas of drug desian, cancer research, and viraloav.
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