Rejuvenation of X-ray data collection facilites at the Institute of Structural Molecular Biology at Birkbeck/UCL

Protein X-ray crystallography consists of shining an intense beam of X-rays at crystals made from a highly pure protein. A small amount of the X-rays are scattered by the crystals and from the scattering pattern, the position of the atoms in the protein can be worked out, and this tells us what the protein looks like. This information is very useful in understanding how the proteins work and is an important method of being able to design drugs that will bind and alter the activity of the protein. There are two types of X-ray source, a synchrotron which is a national or international facility which produces the brightest X-ray beams and an X-ray generator which is based in the university laboratory. The UK is just completing a new synchrotron called Diamond near Didcot. However researchers only get access to these facilities perhaps every couple of months and although they can collect a huge amount of data, it can mean that the feedback to the next set of laboratory experiments can be slow. It is therefore important to have a less intense source in the university laboratory where preliminary characterisation of the crystals can be done and in some cases whole data sets can be collected allowing more rapid feedback to the next set of experiments. We wish to buy a more powerful X-ray generator for use on the university campus. This will allow us to screen crystals of more challenging problems without going to a synchrotron and to collect datasets on a wider range of proteins that we are studying as potential drug targets either for our academic work or in collaboration with small companies in the home counties area.

A new generation of X-ray sources for the home laboratory have been designed with smaller crystals, typical of current macromolecular crystallography, in mind. The generator and mirror combination we wish to purchase has a focal spot size of 70x70 micrometres which is better matched to the size of the sample than the typically 300 micrometre spot size of the equipment we currently have. Coupled with the smaller spot size these generators are able to deliver an order of magnitude more flux. This combination of technical improvements allows the screening of a lot more samples in house with more rapid feedback to improved purification and crystallisation protocols compared to waiting for trips to synchrotrons. Coupled with this it also allows more data collection to be done solely in house. This is particularly suited to screening for small molecules bound to protein crystals as part of a lead compound or lead optimisation programme to produce a drug candidate. We plan to significantly increase the amount of this work we do, both in our academic research and in collaboration with a number of smaller companies in the London and home counties area. A new X-ray source will very significantly improve the productivity of the ISMB at Birkbeck/UCL which is one of the larger groupings of X-ray crystallographers in the UK.