Collaborative Research: ABI Development: Building a Pipeline for Validation, Curation and Archiving of Integrative/Hybrid Models

结构生物学领域的最新进展已经导致使用新的“整合/混合”（I/H）方法来阐明具有高生物影响的非常大的大分子机器的三维结构。这些前沿的I/H方法整合了来自不同来源的信息，以确定复杂生物分子组装体的结构，类似于组装拼图的碎片以构建三维物体。使用I/H方法确定的一些标志性结构包括核孔复合物和蛋白酶体盖子复合物，核孔复合物使蛋白质能够穿过核膜转运，蛋白酶体盖子复合物调节细胞中受损、故障或有毒蛋白质的降解。目前还没有能够将这些I/H结构存档的储存库，因此它们可用于下游科学和生物医学应用。目前的项目建立了一个全面的软件管道，以支持I/H模型的验证、管理和传播，以便更广泛的社区可以免费使用。该项目的成果将使世界各地的研究人员、教育工作者和学生能够接触到生物组装的关键结构。该项目将影响使用结构生物学数据进行研究的科学家以及研究结构在生物学中作用的学生和教育工作者。这项研究将直接和显着提高生物学和医学领域，并通过教育和推广活动扩大其对更广泛的社区的影响。该项目扩展了以前开发的原型系统（PDB-Dev），构建了完整的数据管道，用于I/H模型的管理、验证和交付。这将通过以下方式实现：创建一个自动沉积系统，以支持广泛的I/H模型;利用现有协议和工具，开发用于处理I/H模型的注释和验证管道;开发用于可视化多尺度模型表示和模型不确定性的新工具;创建服务体系结构，以管理能够支持I/H模型和相关实验数据的进化改进的联合资源之间的数据交换;以及开发一个交付平台，以支持数据集发现，并提供用于搜索、报告和数据下载的网络服务。由于I/H方法集成了来自几种实验和计算技术的信息，因此该项目还原型化了一个新的集中式软件环境，该环境有助于结构生物学模型和数据存储库之间的自动通信和数据交换，从而有助于I/H建模。这些发展将导致一个强大的系统，能够存档和传播的I/H模型，以标准的形式向公众。该项目的结果将在PDB-Dev网站www.example.com上提供https://pdb-dev.wwpdb.org.This奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

Recent advances in the field of structural biology have led to the elucidation of the three-dimensional structures of very large macromolecular machines of high biological impact using novel "integrative/hybrid" (I/H) methods. These leading-edge I/H methods integrate information from different sources to determine the structures of complex biomolecular assemblies, analogous to assembling the pieces of a puzzle to build a three-dimensional object. Some of the landmark structures determined using I/H methods include the nuclear pore complex that enables the transport of proteins across the nuclear membrane and the proteasomal lid sub-complex that regulates the degradation of damaged, malfunctioning or toxic proteins in the cell. There is currently no repository capable of archiving these I/H structures so that they are available for downstream scientific and biomedical applications. The current project builds a comprehensive software pipeline to support the validation, curation and dissemination of I/H models so that they are freely available to the broader community. The outcomes of this project will make key structures of biological assemblies accessible to researchers, educators and students around the world. This project will impact scientists who use structural biology data for their research as well as students and educators who study the role of structure in biology. This research will directly and significantly enhance the field of biology and medicine and extend its impact on the broader community through education and outreach activities. This project extends a previously developed prototype system (PDB-Dev) by building the complete data pipeline for the curation, validation and delivery of I/H models. This will be achieved through the creation of an automated deposition system to support a broad range of I/H models; development of annotation and validation pipelines for processing I/H models by leveraging existing protocols and tools; development of new tools for visualizing multi-scale model representations and model uncertainly; creation of a service architecture to manage data exchange among federated resources capable of supporting evolutionary improvements of I/H models and associated experimental data; and development of a delivery platform to support data set discovery and to provide web services for searching, reporting, and data download. Since I/H methods integrate information from several experimental and computational techniques, this project also prototypes a new centralized software environment that facilitates automated communication and exchange of data among a federation of structural biology model and data repositories contributing to I/H modeling. These developments will lead to a robust system capable to archiving and disseminating I/H models to the public in a standard form. The results of the project will be available on the PDB-Dev website at https://pdb-dev.wwpdb.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.