High Throughput Protein Crystallography Using Zone Plate

DESCRIPTION (provided by applicant): The determination of protein structure associated with each gene and functionality is crucial in understanding living systems and will have a significant impact in such areas as protein engineering, recombinant N DA technology and gene therapy. X-ray protein crystallography is probably the most useful technique to determine macromolecule structures such as proteins, especially for molecular weights above about 30kD. Xradia propose a new approach to improve the throughput and operation of lab-based protein diffraction system by the use of a zone plate as the focusing optic and a bright microfocus x-ray source in a compact layout. In Phase I, we will demonstrate the feasibility of the proposed the concept using available a zone plate on an existing protein diffraction system and show that it is will be possible to develop a compact protein crystallography system in Phase II that has a throughput at least 10X better than the current systems and ease of operation in terms of installation and alignment, setting of desirable focusing position between the protein crystal and the detector. In Phase II, we propose to fabricate zone plates with improved performance in both radiation collection angle and focusing efficiency, and construct a prototype compact protein crystallography system using a conventional microfocus x-ray source, zone plate optic, and CCD camera. The expected outcome of this effort is a working prototype of a high-throughput x-ray diffraction system that is also optimized for small (approximately 30 mm) macromolecular crystals that can fit on a benchtop and is easily aligned and operated, and that can be produced for a relatively modest cost. A commercially-available version of this system could dramatically increase the capabilities for crystal selection and data collection in the home lab.