PROJECT SUMMARY (Laboratory for Biomolecular Structure and Function) The OUHSC X-ray Core Facility was initiated in 1998 with a NIH IDeA grant to Dr. Paul Weigel, former chair of the Department of Biochemistry and Molecular Biology. The facility was recently renamed the Laboratory of Biomolecular Structure and Function (LBSF). The LBSF provides expertise and assess to instruments to the individual COBRE projects on a variety of techniques critical to crystallographic and small angle X-ray scattering studies (SAXS) of proteins and nucleic acids. The crystallographic techniques include screening crystals for diffraction quality at room temperature, crystal cryo-protectant screening, crystal cryprotection under high pressure, diffraction data collection, diffraction data processing, space group assignment, structure determination, structure refinement, structure analysis, structure interpretatoin, and figure preparation. The SAXS-related methods include dynamic light scattering to check for aggregates and to measure polydispersity prior to sending the samples for SAXS data colleciton at national facilities. In Phase I of the COBRE, the facility was upgraded with a new Rigaku MicroMax 007 X-ray generator, a plate Wyatt plate-reading dynamic light scattering instrument for high throughput studies, and a Leica microscope for making images of crystals. The new X-ray generator gives a four-fold more intense X-ray beam of smaller diameter. These features are critical for the screening the small, weakly diffracting crystals common in the COBRE research projects. The Oklahoma Medical Research Foundation donated a Mar345 image plate X-ray dectector, a Varimax HF optic system, an Oxford cryosystem, and a MSC Xe-Siter apparatus for introducing noble gases into protien cavities in crystals for phasing experiments. The Rigaku X-ray system was modifed by adding a second bench to enable the addition of the Mar345 system to the second port of the X-ray generator. The RaxisIV system was enclosed with shielding that enables users to mount crystals on the Mar system while data are being collected on the Rigaku system. This setup has enabled two groups to collect data simultaneously or one group to collect diffraction data from two crystals at the same time. The new X-ray generator has been used to screen protein and RNA crystals for diffraction quality and to develop cryo-conditions. The plate-reading DLS apparatus has been used to screen buffers for those that promote protein stability for protein storage and crystallization trials. DLS has also been used to screen SAXS samples for the presence of aggregates prior to shipment to SAXS beam lines at national facilities. In Phase I, ten groups participated in SAXS studies. During Phase II, an Integrative Molecular Modeling Unit will be added to faciltate intenstive computational work such as virutal screening for candidate drug molecules, molecular dynamics simulations, molecular replacement with phenix-rosetta, and mol...