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

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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.