Unified Data Resource for Large Complexes Determined by Cryo-Electron Microscopy

描述（由申请人提供）：冷冻电子显微镜（cryoEM）是结构生物学中一种成熟的方法，可以在2到100 a的宽分辨率范围内确定大分子复合物和细胞的3D结构，其信息弥合了细胞生物学和晶体学/核磁共振之间的差距。现在，结构、分子和细胞生物学家普遍认为，低温电镜图谱及其相关模型可以为后续假设驱动的研究和知识发现奠定基础。在过去的四年里，由位于英国Hinxton的欧洲生物信息学研究所（EBI）和位于美国新泽西州皮斯卡塔威的新泽西州立大学Rutgers的结构生物信息学研究合作实验室（RCSB）组织的几次独立研讨会已经达成了一个共识，即是时候建立公共支持的、一站式的低温电镜密度图、原子模型和相关元数据的沉积和检索设施了。该提案是EBI、RCSB和休斯顿贝勒医学院国家大分子成像中心（NCMI）的研究人员共同努力的结果。这些研究人员在密度图存档（Kim Henrick），原子模型坐标存档（Kim Henrick, Helen Berman）以及低温电子显微镜技术开发的各个方面具有互补的专业知识，包括数据收集，地图生成，低温电子显微镜地图约束建模，可视化，分割和注释（Wah Chiu）。我们建议整合这三个研究中心的专业知识和基础设施，建立一个低温电镜地图、模型及其相关元数据的全球存储和检索网络，以及一个用于标准化地图格式转换、地图分割和评估、模型评估、可视化和数据集成的软件工具的web服务。这些工具对于核查存放的数据是必不可少的，也将有助于有效地利用存档的数据。我们将与cryoEM软件的主要开发人员协商开发这些工具。在包含到web服务集之前，我们将评估这些工具对当前数据资源中可用的地图和坐标数据的预期用途的适用性。我们将完整地记录这些工具的使用和限制。此外，随着该领域的发展和成熟，将以一种易于维护和扩展的方式建立新的、全面的cryoEM数据资源。最后，这项拟议研究的一个重要组成部分活动是在整个资助期间收集社区投入，以便最终系统将以最高标准设计和实施，以满足低温专家和生物最终用户的需求。

DESCRIPTION (provided by applicant): Cryo-electron microscopy (cryoEM) is a maturing methodology in structural biology that enables the determination of 3D structures of macromolecular complexes and cells at a broad range of resolution from 2 to 100 A with information that bridges the gap between cell biology and crystallography/NMR. It is now well accepted by structural, molecular and cell biologists that a cryoEM map and its associated model can form the basis for subsequent hypothesis-driven research and knowledge discovery. In the past four years, several independent workshops organized by the European Bioinformatics Institute (EBI) in Hinxton, UK and the Research Collaboratory for Structural Bioinformatics (RCSB) at Rutgers, the State University of New Jersey, Piscataway, NJ, USA, have reached a community consensus that it is time to establish publicly supported, one-stop deposition and retrieval facilities for cryoEM density maps, atomic models and associated metadata. This proposal is a joint effort among investigators of the EBI, RCSB and the National Center for Macromolecular Imaging (NCMI) at Baylor College of Medicine, Houston. These investigators have complementary expertise in archiving density maps (Kim Henrick), archiving coordinates of atomic models (Kim Henrick, Helen Berman), and all aspects of cryoEM technology development, including data collection, map generation, cryoEM map restrained modeling, visualization, segmentation and annotation (Wah Chiu). We propose to integrate the expertise and infrastructure of the three well-established research centers to create a global deposition and retrieval network for cryoEM maps, models and their associated metadata, as well as a web service for a number of software tools for standardized map format conversion, map segmentation and assessment, model assessment, visualization, and data integration. These tools are essential for verification of the deposited data and would also facilitate efficient use of the archived data. We will develop these tools in consultation with the major developers of cryoEM software. Before inclusion in the set of web services, we will evaluate the suitability of these tools for the intended purposes with the map and coordinate data available in the current data resources. We will fully document the usage and limitations of these tools. Moreover, the new, comprehensive cryoEM data resource will be built in a manner that will be straightforward to maintain and extend as the field grows and matures. Finally, an important component activity of this proposed research is to gather community input throughout the entire grant period so that the final system will be designed and implemented at the highest standards to serve the needs of both cryoEM experts and biological end-users.