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

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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.