Computational Resource for Structural Biology and Molecular Biophysics

华盛顿大学佩雷尔曼医学院的13名研究人员组成的小组 宾夕法尼亚州，包括26个不同NIH拨款中的PI，拨款超过6700,000美元 每年支持，请求资金用于购买计算资源以用于结构 生物学和分子生物物理学。该资源旨在利用现有的 在低温电子显微镜领域工作的仪器和研究小组 EM)，核磁共振，X射线结晶学和散射，单分子生物物理，高分辨率 质谱学(MS)、氢交换(HX)和大分子模拟。一 该资源的职能将是支持Cryo-EM Tecnai G2 F20双200千伏油田 发射枪透射电子显微镜与早先获得的共享 仪器设备补助。该仪器是一个成功且使用良好的EM核心设施的一部分 现在产生数据的速度需要显著更高的吞吐量计算机资源 对于3D图像重建，为了最大限度地提高对Cryo-EM的投资回报。这个 资源专门针对计算密集型任务，这些任务效率不高 在高度分散且已经饱和的计算设施上执行 佩雷尔曼医学院。拟议的硬件将大量使用最先进的设备 图形处理单元(GPU)硬件，已被证明可提供无与伦比的 结构生物学所需的计算类型的每美元性能 分子生物物理学。计算能力最强所需的经过GPU优化的软件 密集的结构生物学和分子生物物理学的应用已经 已开发，因此所需硬件可立即投入使用。主要用户拥有 资金充足的研究项目，解决疾病的重要问题，如 淀粉样变与神经退行性疾病、蛋白质错误折叠疾病、基因 调节蛋白及其在癌症中的异常调节，肌球蛋白缺陷导致 色素减退和神经系统疾病，鉴定和结构表征 药物和治疗的新蛋白质靶点。所请求的计算机资源将大大增加 推进这些重要的生物医学相关项目以及其他研究人员的项目 使用的是低温电磁核。

A group of 13 investigators in the Perelman School of Medicine at the University of Pennsylvania, which includes PI's on 26 different NIH grants, with over $6,700,000 grant support per year, requests funds for the purchase of a computational resource for structural biology and molecular biophysics. The resource is designed to leverage existing instrumentation and research groups working in the areas of Cryo-Electron microscopy (Cryo- EM), NMR, X-ray crystallography and scattering, single molecule biophysics, high resolution mass spectroscopy (MS), Hydrogen Exchange (HX) and macromolecular simulations. One function of the resource would be to support the Cryo-EM Tecnai G2 F20 TWIN 200kV field emission gun transmission electron microscope obtained with an earlier shared instrumentation grant. This instrument, part of a successful and well used EM core facility is now producing data at a rate that requires significantly higher throughput computer resources for 3D image reconstruction, in order to maximize return on the investment in Cryo-EM. The resource is targeted specifically for computationally intensive tasks which cannot be efficiently performed on the highly distributed, and already saturated computing facilities in the Perelman School of Medicine. The proposed hardware will make heavy use of state of the art graphics processing unit (GPU) hardware, which has been shown to provide unmatched performance per dollar on the type of computations required by structural biology and molecular biophysics. GPU-optimized software required for the most computationally intensive structural biology and molecular biophysics applications has already been developed, so the requested hardware could be put into use immediately. Major users have well-funded research programs that address important questions in diseases such as amyloidogenesis and neurodegenerative disorders, diseases of protein-misfolding, gene regulatory proteins and their aberrant regulation in cancer, defects in myosin leading to hypopigmentation and neurological disorders, identification and structural characterization of new protein targets for drugs and therapeutics. The requested computer resources will greatly advance these important biomedically relevant projects as well as those of other investigators using the Cryo-EM core.