Title: High performance, high throughput laboratory x-ray illumination system for protein crystallography Project Summary and Abstract X-ray protein crystallography is the leading method for determining the 3D structures of macromolecules (proteins, viruses, nucleic acids). Structural understanding provides key insight into their functionality and is now an essential tool for industrial applications in food & agriculture, protein engineering, and drug design. This has resulted in several high profile late-stage clinical drug trials for cancer and Alzheimer?s therapeutics. We propose to develop an X-ray illumination system comprising a proprietary x-ray source and x-ray optic optimized for the Single-Wavelength Anomalous Dispersion (SAD) approach to x-ray crystallography. This illumination beam system is designed to deliver x-ray energies that optimize the signal of commonly used scatterers in the SAD technique, and will furthermore provide 8X higher flux than current state-of-the-art laboratory x-ray sources. The key innovations include a novel pattern and new materials for the x-ray source targets and an axially symmetric x-ray optical train that provides a small crossfire for the illumination beam. This proposed phase II project will result in the development of a prototype of the illumination beam system and experimental demonstration of the intended specifications and parameters.
This project proposes to develop a high flux X-ray illumination system for x-ray crystallography, comprising a proprietary x-ray source and a novel x-ray optical train. The intended impact is to enable substantially improved sensitivity and speed for in-laboratory x-ray crystallography determination of protein structures, which is now an essential tool for drug development and food and agricultural applications. Knowledge of protein structures has proven critical for many emerging research topics, including: more efficient approaches of drug design (e.g. for cancer and neurodegenerative diseases), protein engineering, and optimization of toxic waste removal through bacterial bioremediation.
