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导致了使用新颖的“整合/杂交”（I/H）方法来阐明具有高生物影响的超大型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合的结构，类似于将拼图碎片组装成三维物体。使用I/H方法确定的一些具有里程碑意义的结构包括核孔复合物（使蛋白质能够通过核膜运输）和蛋白酶体盖子亚复合物（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结构存档的存储库，以供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，使它们能够免费提供给更广泛的社区。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。这个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的作用的学生和教育工作者。这项研究将直接和显著地加强生物和医学领域，并通过教育和推广活动扩大其对更广泛社区的影响。该项目通过为I/H模型的管理、验证和交付构建完整的数据管道，扩展了先前开发的原型系统（PDB-Dev）。这将通过创建一个自动化沉积系统来实现，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；多尺度模型表示和模型不确定性可视化新工具的开发创建服务体系结构，以管理能够支持I/H模型和相关实验数据的渐进式改进的联合资源之间的数据交换；并开发一个交付平台来支持数据集发现，并提供用于搜索、报告和数据下载的web服务。由于I/H方法集成了来自多种实验和计算技术的信息，该项目还原型化了一个新的集中式软件环境，该环境促进了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，有助于I/H建模。这些发展将导致一个强大的系统，能够以标准形式向公众存档和传播I/H模型。该项目的结果将在PDB-Dev网站（https://pdb-dev.wwpdb.org.This）上公布。该奖项反映了美国国家科学基金会的法定使命，并通过基金会的知识价值和更广泛的影响审查标准进行评估，认为值得支持。

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.