An e-Science Resource for High Throughput Protein Crystallography

The aim of this project is to make it routine to obtain reliable information on protein structure using X-ray crystallography in a high-throughput mode by introducing easy access to all facilities together with automation where appropriate. This will allow the biologist to concentrate on the scientific questions rather than the technical details. Scientific Background The vast amounts of data coming from the genome projects have generated a demand for new methods to determine structural and functional information about the proteins and other macromolecules in living systems. At the same time, advances in biotechnology are making it easier to obtain pure samples of these molecules. This has led to a demand for, and the possibility of, high throughput structural biology and has given rise to the term “structural genomics”. High-throughput techniques also open up the possibility of carrying out mass binding studies on each protein in order to investigate possible function or to develop inhibitors as potential pharmaceutical compounds or functional probes. Increasingly, scientists who are not experts in the various techniques individually will carry out the complete investigations. It is vital that high-throughput techniques do not lead to a reduction in the quality of the information obtained. In the UK, several large projects involving high throughput protein structure determination using crystallographic methods have recently started or been announced. As an example, the recently announced BBSRC SPORT initiative has, as one of its aims to "establish in the UK an internationally competitive capability in high throughput, parallel approaches to the expression, isolation, purification and structure/ function determination of biological macromolecules. This capability must be achieved as part of a programme aimed at producing detailed descriptions of the structure and molecular functions of cellular complexes and/or pathways of major biological importance." The diagram underneath shows the major steps in a protein crystallography project from selecting the target protein to investigate to depositing and analyzing the structure. Aims of the Project A large amount of information will be generated by this work. This information will have to be passed through the structure determination process and stored in accessible databases so that functional information can be obtained and experiments repeated, perhaps with modifications. Many of the investigations will be initiated and carried out by biologists with little experience in physical techniques such as x-ray crystallography. Where applicable, automation of experiments and data analysis will be necessary. It is therefore essential that reliable methods of handling and analysing the large amounts of data generated by high throughput protein crystallography are developed if the appropriate benefits are to be realised. Protein Production Crystallisation Data Collection Phasing