The Protein Circular Dichroism Data Bank, the DichroWeb Server, and ValiDichro: Data Sharing, Analysis and Standards Resources for CD Spectroscopy

圆二色性（CD）光谱是结构生物学中广泛使用的方法，用于确定蛋白质二级结构，检测与不同条件（如配体结合）相关的构象变化，以及检查大分子相互作用和蛋白质折叠。它经常在大量学术和工业实验室中用作基本表征方法，并且是监管机构指定用于表征生产用于人类的药物蛋白质的方法。同步辐射圆二色性（SRCD）光束线在世界范围内的发展进一步扩展了这种光谱技术的实用性和应用。该提案是为了更新生物信息学和生物资源基金项目“支持蛋白质圆二色性数据库和DichroWeb分析服务器”，该项目迄今为止已经创建了用于数据共享的蛋白质圆二色性数据库（PCDDB），运行了分析网络服务器DichroWeb，并提高了数据质量标准和验证协议。该项目的目的是加强和维护这些由学术和工业结构生物学和生物信息学社区使用的CD光谱学的综合电子存档和分析资源，并开发新的结构生物学分析工具。该项目包括逐步开发、管理和运营PCDDB，这是一个可搜索和下载的沉积数据库，使公众能够免费获取CD数据。这个数据库于今年早些时候开始运作，在世界范围内是独一无二的。它提供了公共存档和搜索设施，以开放访问圆二色谱光谱和元数据，很大程度上以蛋白质数据库（PDB）的方式，蛋白质晶体和NMR数据的长期存在和宝贵的参考数据库资源。这项建议将支持根据我们在操作PCDDB时获得的经验和用户反馈对PCDDB进行持续开发、增强和修改，并使其能够作为一个持续的用户资源运行。该项目还包括升级和继续运行DichroWeb，这是一个用户友好的广泛使用的在线服务器，用于分析圆二色性数据。此外，它还包括为新型分析开发一套新的支持工具（包括跨方法的），为所有商业CD仪器和SRCD光束线创建通用数据格式，验证软件（指导数据采集和处理的质量标准，并确保PCDDB条目的完整性），以及“一站式”服务器，提供处理，分析，显示，和沉积工具（从而简化和改善非专家团体对CD光谱学的使用，并为常规CD用户加速这些过程）。这些项目得到了英国和国际用户社区的大力支持，正如提案中所附的支持信所示。 这些生物信息学资源一起为学术和工业结构生物学和生物信息学社区提供了CD光谱学的全面支持和支持工具包。

Circular Dichroism (CD) spectroscopy is a widely used method in structural biology for determining protein secondary structure, detecting conformational changes associated with different conditions such as ligand binding, and examining macromolecular interactions and protein folding. It is regularly used as a fundamental characterisation method in a large number of both academic and industrial laboratories and is a method designated by regulatory authorities for the characterisation of pharmaceutical proteins produced for use in humans. The worldwide development of Synchrotron Radiation Circular Dichroism (SRCD) beamlines has further extended the utility and applications of this spectroscopic technique. The proposal is for a renewal of the Bioinformatics and Biological Resources Fund project "Support for the Protein Circular Dichroism Data Bank and the DichroWeb Analysis Server", which thus far has enabled the creation of the Protein Circular Dichroism Data Bank (PCDDB) for data sharing, the operation of the analysis webserver DichroWeb, and the advancement of data quality standards and validation protocols. This project's aims are to enhance and maintain these comprehensive electronic archiving and analysis resources for CD spectroscopy that are used by the academic and industrial structural biology and bioinformatics communities and to develop new analysis tools for structural biology. The project includes the progressive development, curation, and operation of the PCDDB, a searchable and downloadable deposition data bank enabling free public access to CD data. This data bank was opened for operation earlier this year and is unique world-wide. It provides public archiving and search facilities for open access to circular dichroism spectral and metadata, much in the manner of the Protein Data Bank (PDB), a long-existing and valuable reference data bank resource for protein crystal and NMR data. This proposal would support continuing development, enhancements, and modifications to the PCDDB based on our experiences gained in operating it and user feedback, as well as enabling it to be run as an ongoing user resource. The project also includes the upgrading and continued operation of DichroWeb, a user-friendly widely-used online server for the analysis of circular dichroism data. In addition, it includes the development of a new suite of support tools for novel types of analyses (including cross-methodological ones), creation of common data formats for all commercial CD instruments and SRCD beamlines, validation software (to guide quality standards of data acquisition and processing, and ensure the integrity of PCDDB entries), and a "one-stop-shop" server providing a pipeline for processing, analysis, display, and deposition tools (thereby simplifying and improving the use of CD spectroscopy by the non-expert community, and the speeding up of these processes for regular CD users). These projects have strong support from the UK and international user communities as indicated by the letters of support included with the proposal. Together these bioinformatics resources provide a comprehensive package of enabling and supportive tools in CD spectroscopy for the academic and industrial structural biology and bioinformatics communities.