SBIR Phase II: New Convergent X-Ray Beam Based System for Protein Crystallography

这个小型企业创新研究(SBIR)二期项目将开发一种新的基于会聚X射线束的结晶学系统，用于测量蛋白质晶体的质量和结构，以努力支持晶体生长开发工作，并作为在专用同步加速器的大分子结构设施中进行精细、高分辨率结构确定之前对非常小的蛋白质晶体进行预筛选的工具。对多种晶体类型、大小和完美程度的测量将在纽约州卫生局沃兹沃斯中心的活性蛋白质晶体生长和表征实验室进行。为了检验会聚光束法(CBM)的潜在优点和局限性，本实验室将使用相同的晶体进行平行测量，并使用最先进的蛋白质衍射系统。还将在工业实验室中进行测量，以评估CBM作为一种商业、紧凑、高强度、低功率、低成本的蛋白质筛选仪器的潜力。该项目的商业应用将在结构蛋白质组学领域。开发一种紧凑、高效、高灵敏度的小蛋白质晶体质量和初步结构测量系统，对于实现人类和非人类基因组学最新进展提供的巨大机遇至关重要，这将在疾病治疗和药物发现领域产生深远影响。此外，这样的系统可以在学术、科学和工业项目中找到广泛的应用，用于冶金、地质、环境和生物或其他材料的结构、织构和应变的高分辨率显微观察。

This Small Business Innovation Research (SBIR) Phase II project will develop a new convergent x-ray beam based crystallography system for measurement of the quality and the structure of protein crystals in an effort to support crystal growth development efforts and as a prescreening tool for very small protein crystals prior to refined, high-resolution structure determination at dedicated synchrotron-based macromolecular structure facilities. Measurements of a broad range of crystal types, sizes, and degrees of perfection will be carried out in an active protein crystal growth and characterization laboratory at the Wadsworth Center of the New York State Health Department. Parallel measurements using the same crystals will be made in this laboratory with a conventional state-of-the-art protein diffraction system in order to examine the potential benefits and limitations of the convergent beam method (CBM). Measurements will also be made in an industrial laboratory to evaluate the potential of CBM as a commercial, compact, high-intensity, low-power, low-cost, protein screening instrumentation. The commercial application of this project will be in the area of structural proteomics. Development of a compact, high-efficiency, high-sensitivity system for measurement of the quality and preliminary structure of small protein crystals is crucial to implementation of the huge opportunities offered by recent advances in human and non-human genomics, with far-reaching consequences in the areas of disease therapy and drug discovery. Furthermore, such a system could find broad applications in academic, scientific and industrial programs for high- resolution microscopy of structure, texture, andstrain in metallurgical, geological, environmental and biological or other materials.