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

圆二色谱(CD)是结构生物学中广泛使用的一种方法，用于确定蛋白质的二级结构，检测与配体结合等不同条件相关的构象变化，以及研究大分子相互作用和蛋白质折叠。它经常被用作大量学术和工业实验室的基本表征方法，也是监管当局指定的用于人类生产的药用蛋白质的表征方法。同步辐射圆二色谱(SRCD)光束线在世界范围内的发展进一步扩大了这一光谱技术的用途和应用。该提案是关于延长生物信息学和生物资源基金“支持蛋白质圆二色谱数据库和DichroWeb分析服务器”的项目，该项目迄今已使建立蛋白质圆二色谱数据库(PCDDB)用于数据共享、运行分析Web DichroWeb服务器以及改进数据质量标准和验证协议成为可能。该项目的目的是加强和维护学术和工业结构生物学和生物信息学社区使用的这些用于CD光谱学的全面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、管理和运作PCDDB，这是一个可搜索和可下载的沉积数据库，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通运行，在世界范围内是独一无二的。它为开放获取圆二色谱和元数据提供了公共存档和搜索设施，很像蛋白质数据库(PDB)，这是一个长期存在的、有价值的蛋白质晶体和核磁共振数据参考数据库资源。这项建议将支持根据我们在操作过程中获得的经验和用户反馈对PCDDB进行持续发展、改进和修改，并使其能够作为持续的用户资源运行。该项目还包括升级和继续运营DichroWeb，这是一种用户友好的、广泛使用的用于分析圆二色数据的在线服务器。此外，还包括为新型分析(包括跨方法分析)开发一套新的支持工具，为所有商用CD仪器和SRCD光束线创建通用数据格式，验证软件(以指导数据采集和处理的质量标准，并确保PCDDB条目的完整性)，以及提供处理、分析、显示和沉积工具管道的“一站式”服务器(从而简化和改进非专家群体对CD光谱学的使用，并加快CD常规用户的这些过程)。提案中的支持函表明，这些项目得到了英国和国际用户群体的大力支持。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一套全面的CD光谱学支持和支持工具。

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.