A Large-area Pixel Array Detector System for Macromolecular Crystallography

描述（由申请人提供）：通过x射线大分子晶体学获得的高分辨率，三维原子分辨率结构为蛋白质，核酸及其高阶复合物的分子机制提供了基本的见解。这些信息对于解释从基因组测序工作中获得的大量一维序列数据至关重要，例如，了解遗传突变对蛋白质功能的影响，以及开发治疗一系列疾病所需的治疗剂，包括许多癌症、神经系统疾病、艾滋病毒和其他病原体。在过去的30年里，基于同步加速器的x射线生成技术的进步，加上检测和数据收集硬件和软件的进步，推动了大分子晶体学的爆炸式增长，并使结构生物学家能够解决基本的和日益复杂的生物医学问题。x射线探测器技术的突破使衍射数据的测量能够在更大的动态范围内，在更大的探测区域内，以更低的背景和更快的速度进行。这些特征对于测量弱衍射晶体和/或具有大型大分子复合物和膜蛋白特征的非常大的单位细胞晶体的数据是必不可少的。下一代技术，像素阵列探测器（PAD），基于硅传感器的固态阵列，可以感知x射线光子并直接输出电信号，而不需要x射线到可见光的中间转换。该申请是一个完整的大分子晶体学探测器系统的请求，包括由Dectris公司制造的PILATUS 6M像素阵列探测器（PAD），以及相关的控制、数据采集、数据处理和存储计算硬件。该系统将安装在斯坦福同步辐射光源（SSRL）的光束线11-1 （BL11-1）上。与目前可用的CCD探测器相比，PILATUS 6M PAD具有许多优点，包括优越的信噪比、改进的图像吞吐量、增加的检测面积和更大的动态范围。该探测器非常适合高通量多波长异常衍射（MAD）、精细切片实验和通过衍射快速对准晶体，这将需要在具有挑战性的生物医学重要系统中推动BL11-1研究的前沿。它将为NIH资助的研究人员保持国际竞争力，并将有助于留住员工和维持工作岗位。

DESCRIPTION (provided by applicant): High-resolution, three-dimensional atomic resolution structures obtained by x-ray macromolecular crystallography provide fundamental insights into the molecular mechanisms of proteins, nucleic acids, and their higher-order complexes. This information is essential for interpreting the explosion of one-dimensional sequence data obtained from genome sequencing efforts, for example understanding the effects of inherited mutations on the function of proteins, as well as for development of therapeutic agents needed to combat a range of diseases, including many cancers, neurological conditions, and HIV and other pathogens. Advances in synchrotron-based x-ray generation, coupled with advances in detection, and data collection hardware and software, have fueled the explosive growth of macromolecular crystallography over the last 30 years, and have enabled structural biologists to address and solve fundamental and increasingly complex biomedical problems. Breakthroughs in x-ray detector technology have enabled measurement of diffraction data over a larger dynamic range, in a larger detective area, and with lower background and greater speed. These features are essential for measuring data from weakly diffracting crystals and/or from crystals with very large unit cells characteristic of large macromolecular complexes and membrane proteins. A next generation technology, the Pixel Array Detector (PAD), is based on a solid-state array of silicon sensors that sense x-ray photons and directly output an electrical signal, rather than requiring an intermediate conversion of x-rays to visible light. This application is a request for a complete detector system for macromolecular crystallography, consisting of a PILATUS 6M Pixel Array Detector (PAD) manufactured by Dectris, Inc., and associated control, data acquisition, data handling and storage computing hardware. This system will be installed on beam line 11-1 (BL11-1) at the Stanford Synchrotron Radiation Light source (SSRL). The PILATUS 6M PAD offers many advantages over the presently available CCD detectors including superior signal-to-noise, improved image throughput, increased detection area and larger dynamic range. The detector is well suited for high-throughput Multi-wavelength Anomalous Diffraction (MAD), fine-phi-slicing experiments, and rapid alignment of crystals by diffraction that will be needed to drive the forefront of BL11-1 research on challenging biomedically important systems. It will maintain international competitiveness for NIH funded researchers and will contribute to retaining staff and maintaining jobs.