EXCEED THE SPACEPROVIDED.Synchrotron radiation (SR) is an extremely bright and tunable x-ray source that enables forefront research instructural molecular biology (8MB). A 'Synchrotron Structural Biology Resource' is supported at theStanford Synchrotron Radiation Laboratory (SSRL) by the NIH and DOE to develop technologies inmacromolecular crystallography, x-ray absorption spectroscopy and small angle x-ray scattering/diffractionand to disseminate these methodologies for use in the biomedical research community. This proposal is forthe continued funding, operation and further development of this Resource. Newinitiatives will capitalize onthe remarkable enhancement in SRperformance resulting from the completed upgrade of the SSRL storagering to a 3d'generation source (SPEARS). Proposed also is a new focus on SMB applications of ultrashortpulse, ultrabright x-rays from what willbe the world's first x-ray free-electron laser (LCLS) beingpioneeredatSLAC. A principal aim is to optimize experimental facilities, detectors, software and computer capacity onthe 9+ SMB beam lines at SSRL (and a 10th in construction) to take full advantage of the increasedbrightness provided by SPEARS. This will enable the Resource to advance the scientific forefront with newinitiatives built upon novel instrumentation (especially advanced detectors), innovative software andautomated/high-throughput systems for: studying high resolution structures of large, complexmacromolecules, including molecular machines; imaging the spacial distribution and chemical nature ofelements in non-crystalline biological materials; investigating fundamental questions in biophysics such asprotein and RNA folding; developing and improving methods for imaging non-crystalline biological materialsat near atomic resolution; and studying very fast time-resolved structural changes in chemical and biologicalsystems with ultrafast absorption and scattering techniques. These scientific advancements will befacilitated by parallel developments in software to provide expanded capabilities for instrument and detectorcontrol, remote data collection and real-time data analysis. Strong collaborative research programs involvinga large number of outside scientists will drive and support core technological developments. Relevance is toa number of important biological problems including the structure of enzymes, metalloproteins, membrane-bound proteins and immunoglobulins; the active site structure of metalloproteins involved in oxygenmetabolism, nitrogen fixation, and photosynthesis; and how these structures change in different states orevolve in time as reactions or events like protein folding or conformational changes occur. Such informationis more broadly important to the health-related areas of drug desian, cancer research, and viraloav.
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