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

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.

Circular Dichroism (CD) spectroscopy is used in structural biology for determining protein secondary structure, detecting conformational changes, and examining macromolecular interactions and protein folding, and is a method designated by regulatory agencies for the characterisation of pharmaceutical proteins for human use.
This proposal is to enhance, curate and operate a comprehensive set of electronic archiving and analysis resources for CD spectroscopy.
It includes the Protein Circular Dichroism Data Bank (PCDDB), a deposition, searchable and downloadable data bank of CD spectra, which began operation earlier this year. The aim of the data bank is to provide public archiving facilities and open access to validated circular dichroism spectral and metadata. The project would support continuing development, enhanced functionalities and modifications based on our experience gained in operating it and user feedback, as well as enabling it to be run as an ongoing user resource. The project also includes enhancements to, and operation of, DichroWeb, a widely-used online server for the analysis of circular dichroism data.
This proposal includes the development of a suite of support tools for novel types of CD analyses based on data deposited in the data bank, including spectral nearest neighbour identification, spectral matching (with applications in bioprocessing), and back calculations of spectra from crystallographic coordinates. It will also include enhanced validation software (establishing standards for spectroscopic data and ensuring the data quality in the PCDDB). A further development will be a one-stop-shop CDpipeline server that will incorporate processing, display, analyses, validation and deposition (aiding casual users of the method as well as improving throughput for more advanced users).
Together these bioinformatics resources will provide enabling and supportive tools in CD spectroscopy for the structural biology and bioinformatics communities.

Circular dichroism (CD) spectroscopy is a widely used technique in structural biology. The resources proposed would benefit those who utilise CD in both academia and the commercial sector. Because CD is a spectroscopic technique currently meeting ICH Guidelines for characterisation of pharmaceuticals for human use, there has already been significant interest in the tools described in this proposal expressed by the pharmaceutical industry, SMEs and regulatory agencies such as the European Medicines Agency and the US Food and Drug Administration. The Protein Circular Dichroism Data Bank archive will be a resource for well-characterised protein spectra and can be a traceable resource for documentation of medicinal proteins (for bioprocessing and biosimilars comparisons). The validation tools and spectral comparisons and metrics tools to be developed will have value in protein characterisations and quality evaluations, and DichroWeb has already proven to be a useful tool by big pharma, SME and food industry users.