Collaborative Research: ABI Development: Building a Community Gateway for Cryo-Electron Microscopy Structure Determination

结构生物学是一个致力于理解生命的化学基础的领域，由于在过去的4年里，低温电子显微镜（cryo-EM）作为一种能够产生原子分辨率结构的技术的出现，正在经历一场革命。这种“分辨率革命”将以前其他结构生物学技术无法企及的结构置于触手可及的范围内。因此，科学家们对低温电子显微镜的扩展能力越来越感兴趣。虽然前几代cryo-EM用户熟悉Linux和处理数据所需的HPC工具，但现在许多结构生物学家对这项技术感兴趣，情况并非如此。我们认为这是冷冻电镜技术发展的主要障碍。为了消除这一障碍，该项目将开发一个易于使用的网络平台，或“科学网关”，该平台将与高性能计算资源、数据处理算法和长期数据存储选项相连接，使没有经验的用户能够充分利用低温电镜的潜力。一个原型网关（COSMIC2：用于云计算的Cryo-EM开源多平台基础设施）已经与圣地亚哥超级计算机中心（SDSC）合作开发，利用其大量的HPC资源。这个项目将把这个早期的原型变成一种资源，将使全国的结构生物学社区受益，并勾勒出一个完全开发的门户的所有特征。提出的COSMIC2网关将通过XSEDE分配给pi，为cryo-EM用户提供大量的计算时间池；一个易于使用的门户网站，允许用户选择低温电镜分析例程；新颖的算法简化数据处理，消除人工用户干预；通过web界面查看输出数据的机制；以及通过将COSMIC2连接到云存储提供商（例如谷歌Drive， Box）的长期数据存储解决方案。COSMIC2网关将最佳地安装和测试主要的低温电镜数据处理软件，以确保它们有效地利用计算资源。该项目的变革性影响将来自于广泛的结构生物学社区对COSMIC2网关的采用，它将为其带来国家高性能计算资源和低温电镜的力量，同时消除访问它们的任何障碍。目前的资源原型可以在http://cosmic-cryoem.org/.This上看到，该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Structural biology, the field devoted to understanding the chemical underpinnings of life, is undergoing a revolution due to the emergence, over the last 4 years, of cryo-electron microscopy (cryo-EM) as a technique capable of producing atomic-resolution structures. This "resolution revolution" has placed within reach structures that were previously inaccessible with other structural biology techniques. As a consequence, there is a growing interest among scientists in the expanded capabilities of cryo-EM. While previous generations of cryo-EM users were familiar with Linux and the HPC tools necessary to process the data, this is not the case with many of the structural biologists now attracted to the technique. We see this as a major barrier to the growth of cryo-EM. In order to remove this barrier, this project will develop an easy-to-use web platform, or "science gateway", that will interface with HPC resources, data processing algorithms, and long-term data storage options, allowing inexperienced users to access the full potential of cryo-EM. A prototype gateway (COSMIC2: Cryo-EM Open Source Multiplatform Infrastructure for Cloud Computing) has been developed in collaboration with the San Diego Supercomputer Center (SDSC), using its substantial HPC resources. This project will turn this early prototype into a resource that will benefit the structural biology community nationwide and outline all the features of a fully-developed gateway. The proposed COSMIC2 gateway will provide a large pool of computing time for cryo-EM users through an XSEDE allocation to the PIs; an easy-to-use web portal allowing users to select cryo-EM analysis routines; novel algorithms to streamline data processing, removing manual user intervention; mechanisms for viewing output data through the web interface; and long-term data storage solutions by connecting COSMIC2 to cloud storage providers (e.g. Google Drive, Box). The COSMIC2 gateway will optimally install and test major cryo-EM data processing software to ensure that they are using computational resources efficiently. The transformative impact of this project will come from the adoption of the COSMIC2 gateway by the broad structural biology community, to which it will bring national HPC resources and the power of cryo-EM while the removing any obstacles in accessing them. The current prototype for the resource may be seen at http://cosmic-cryoem.org/.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.