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.
