THE APPLICATION OF SOLUTION X-RAY SCATTERING TO HIGH-THROUGHPUT STRUCTURAL STUDI

Stanford University, Stanford CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose to study protein targets emerging out of the purification stage of a high-throughput structural crystallography pipeline by solution x-ray scattering. Our effort will focus on a subset of structural genomics targets that were successfully purified but did not yet provide structural data. Our ultimate goal is to obtain molecular envelopes ab initio for those targets, especially large protein complexes. Additional knowledge obtained on quaternary structure equilibrium and interparticle interaction obtained by x-ray scattering will be highly valuable for refining crystallization conditions. As a control, sample targets that provided structural data will also be studied to establish a baseline. Experience with highthroughput methods development, a sample library of >9000 macromolecules, and raw computing power available at the Hauptman-Woodward Medical Research Institute will be combined with a state-of-the-art beamline 4-2 and 96-well, platebased, small angle X-ray scattering expertise at SSRL to utilize solution x-ray scattering as a complementary, highthroughput technique to obtain valuable structural information.