CIBR 19-BBSRC-NSF/BIO: Next generation PDB - FACT infrastructure with value added FAIR data supporting diverse research and education user communities

美国RCSB蛋白质数据库/欧洲蛋白质数据库合作项目的愿景是改善蛋白质数据库中存储的三维（3D）大分子结构信息的数据沉积、传递和管理。这项工作将使自然科学、物理科学和工程科学领域的研究人员、教育工作者及其学生受益。“形状（意思是形状/三维结构）决定了生物学中的功能”——这一观点首次在沃森和克里克发表的DNA双螺旋结构论文中被揭示出来。自从他们具有里程碑意义的发现以来，生物学家，物理学家，化学家和工程师的跨学科合作团队已经生成了约160,000个实验确定的蛋白质和核酸的3D结构，这些结构集中存储在称为蛋白质数据库（PDB）的公共数据资源中。PDB成立于1971年，是第一个开放获取的生物学数字数据资源，现已增长了2万多倍，成为全球单一的档案，包含丰富注释的蛋白质、DNA和RNA的3D结构。这个公共领域的3D结构数据资源对基础生物学、生物医学、生物技术和生物能源产生了巨大的影响，使人们能够从原子水平上理解自然发生的和工程生物分子，并促进了美国食品和药物管理局（fda）在2010-2016年间批准的近90%新药的发现。今天，新的PDB结构来自大分子晶体学（MX），核磁共振波谱学（NMR），单粒子冷冻电子显微镜（3DEM）和微晶体电子衍射（microED）。x射线自由电子激光和用于结构测定的新的综合方法正在加速生物医学研究，在原子水平上深入了解更复杂的生物系统。低温电子断层扫描甚至允许研究在冷冻细胞内“被捕获”的大分子机器。自2003年以来，全球蛋白质数据库（wwPDB, wwpdb.org）合作伙伴关系根据公平-准确-保密-透明的FACT原则和可查找性-可访问性-互操作性-可重用性的FAIR原则，将PDB核心档案（以下简称PDB档案）作为全球公共产品进行管理。wwPDB包括美国（结构生物信息学蛋白质数据库研究合作实验室，RCSB PDB），欧洲（欧洲蛋白质数据库，PDBe）和亚洲（日本蛋白质数据库，PDBj）的本地资助合作伙伴，以及专业的核磁共振资源（BioMagResBank， BMRB）。wwPDB还使美国、欧洲和亚洲之间能够公平地分担PDB数据存档和管理成本。2019年，RCSB PDB、PDBe和PDBj使用基于web的全球wwPDB OneDep软件系统进行沉积、验证和生物固化，共同处理了13377个进入PDB存档的新结构。此外，在2019年，RCSB PDB、PDBe和PDBj共同实现了全球数百万用户下载约8亿个PDB结构数据文件。如今，wwPDB合作伙伴正面临着重大的软件工程挑战，这主要是由于(i)新沉积的MX和3DEM结构的数量和尺寸/复杂性的不断增长，以及（ii）需要管理来自使用x射线自由电子激光器（XFEL）和3DEM的连续飞秒x射线晶体学（SFX）的相关结构（或调查）的输入数据。

The vision of this US RCSB Protein Data Bank/Protein Data Bank in Europe collaborative project is to improve data deposition, delivery, and management of three-dimensional (3D) macromolecular structure information stored in the Protein Data Bank. This work will benefit researchers, educators, and their students across the natural, physical, and engineering sciences."Form (meaning shape/3D structure) dictates function in biology" - was first revealed in the Watson and Crick publication of the DNA double helix structure. Since their landmark discovery, interdisciplinary collaborative teams of biologists, physicists, chemists, and engineers have generated ~160,000 experimentally determined 3D structures of proteins and nucleic acids, which are centrally stored in a public data resource known as the Protein Data Bank (PDB). Founded in 1971 as the first open-access digital data resource in biology, the PDB has grown more than 20,000-fold to become the single global archive housing richly annotated 3D structures of proteins and DNA and RNA. This public-domain 3D structure data resource has had an enormous impact on fundamental biology, biomedicine, biotechnology, and bioenergy by enabling atomic-level understanding of naturally-occurring and engineered biomolecule, and by facilitating discovery of nearly 90% of the new drugs approved by the United States (US) Food and Drug Administration between 2010-2016. Today, new PDB structures are coming from macromolecular crystallography (MX), nuclear magnetic resonance spectroscopy (NMR), single-particle cryo-electron microscopy (3DEM), and micro-crystal electron diffraction (microED). X-ray free electron lasers and new integrative methods for structure determination are accelerating biomedical research with insights into ever more complex biological systems at the atomic level. Cryo-electron tomography even allows studies of macromolecular machines "caught in the act" inside frozen cells.Since 2003, the Worldwide Protein Data Bank (wwPDB, wwpdb.org) partnership has managed the PDB Core Archive (hereafter PDB archive) as a global Public Good according to the FACT principles of Fairness-Accuracy-Confidentiality-Transparency and the FAIR principles of Findability-Accessibility-Interoperability-Reusability. The wwPDB includes locally-funded partners in the US (Research Collaboratory for Structural Bioinformatics Protein Data Bank, RCSB PDB), Europe (Protein Data Bank in Europe, PDBe) and Asia (Protein Data Bank Japan, PDBj), plus a specialist NMR resource (BioMagResBank, BMRB). The wwPDB also enables equitable sharing of PDB data archiving and management costs between US, Europe, and Asia. In 2019, RCSB PDB, PDBe, and PDBj jointly processed 13,377 new structures coming into the PDB archive using the web-based, global wwPDB OneDep software system for deposition, validation, and biocuration. Also, in 2019, RCSB PDB, PDBe, and PDBj jointly enabled download of ~800 million PDB structure data files by millions of users from around the world.Today, wwPDB partners are confronting significant software engineering challenges, resulting from(i) the relentless growth in the number and size/complexity of newly deposited MX and 3DEM structures, and (ii) the need to manage incoming data as groups of related structures (or investigations) coming from serial femtosecond X-ray crystallography (SFX) using X-ray Free Electron Lasers (XFEL) and 3DEM.