Computational Resource for Structural Biology and Molecular Biophysics

一个由13名研究人员组成的研究小组在宾夕法尼亚大学佩雷尔曼医学院进行了研究。 宾夕法尼亚州，其中包括PI的26个不同的NIH赠款，超过670万美元的赠款 每年的支持，要求资金购买计算资源的结构 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（低温， EM）、NMR、X射线晶体学和散射、单分子生物物理学、高分辨率 质谱（MS）、氢交换（HX）和大分子模拟。一 资源的功能是支持Cryo-EM Tecnai G2 F20 TWIN 200 kV电场 发射枪透射电子显微镜获得了较早的共享 仪器补助金。该仪器是成功且使用良好的EM核心设施的一部分， 现在以需要显著更高吞吐量的计算机资源的速率产生数据 用于3D图像重建，以最大限度地提高Cryo-EM的投资回报。的 资源是专门针对计算密集型任务，不能有效地 在高度分布的，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技术 图形处理单元（GPU）硬件，已被证明可以提供无与伦比的 结构生物学所需计算类型的每美元性能， 分子生物物理学GPU优化的软件， 密集的结构生物学和分子生物物理学应用已经 因此，所要求的硬件可以立即投入使用。主要用户有 资金充足的研究项目，解决疾病中的重要问题， 淀粉样变性和神经变性疾病，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，肌球蛋白的缺陷导致 色素减退和神经系统疾病的鉴定和结构表征 药物和治疗的新蛋白质靶点。所请求的计算机资源将大大 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 使用冷冻电磁核心

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.