Fold recognition by synchrotron radiation circular dichroism spectroscopy: a new tool for structural proteomics and structural molecular biology

The three dimensional structures of proteins define their functional properties. At the present time, circular dichroism spectroscopic methods can be used to examine the structures of proteins in solution at the level of secondary (local) structure. This proposal is to develop a new methodology to extend the information content using lower wavelength data. Such a method will provide complementary informtion to that produced by new programmes in structural proteomics being developed in the UK and abroad, especially as it will provide structural information at the level of architecture and fold motifs to be derived from very small amounts of proteins, including those that do not crystallise. In addition, as the UK has invested in a new third-generation synchrotron light source, Diamond, which will have a circular dichroism station as one of its early beamlines, this proposal will provide a new application and means of extracting extra information from the data collected on that beamline.

This is a proposal to develop a new tool for protein structure examination based on synchrotron radiation circular dichroism (SRCD) spectroscopy and to develop methods of analysis that will also have applications for other types of spectroscopy. It will take advantage of the additional low wavelength data available in 'fingerprint' region of SRCD spectra arising from through-space charge transfer transitions, to produce additional information on protein structure beyond the secondary structural information obtainable with conventional circular dichroism spectroscopy. It aims to augment structural proteomics programmes with respect to target selection and modelling, and could provide information on 'low hanging fruit' which express but do not readily crystallise, and a new means of classification of homologous protein structures. Furthermore, it will be a new application that will take advantage of the state-of-the-art beamline which is being built at the Diamond synchrotron, which will follow one from the SRCD station recently commissioned at Daresbury. This will be part of a development programme in SRCD spectroscopy that is enabling the UK to establish a world-leading position in this new technology.