Daresbury Laboratory
Keckwick Lane, Daresbury
Warrington, Cheshire
WA4 4AD (UK)  

c.nave@dl.ac.uk
(44) 1925 603265
(44) 1925 603124

An e-science resource for high throughput protein crystallography (www.e-htpx.ac.uk)

The aim is to unify the procedures of protein structure determination into a single all encompassing interface from which users can initiate, plan, direct and document their experiment either locally or remotely from a desktop computer. The parts of the project based at Daresbury Laboratory are those associated with automating the collection of diffraction data, developing parallel processing algorithms for rapid feedback on the success of the data collection and providing Grid enabled access to all procedures for both academic and industrial scientists. This part of the project involves staff from various groups at the SRS, the Collaborative Computational Project for Protein Crystallography CCP4, www.ccp4.ac.uk) and the CCLRC e-science centre (http://www.e-science.clrc.ac.uk/web/). Other developments are based at BM14 at the ESRF (http://www.bm14.ac.uk), York University Structural Biology Laboratory (http://www.yorvic.york.ac.uk), the European Bioinformatics Institute (http://www.ebi.ac.uk) and the Oxford Protein Production facility (http://www.strubi.ox.ac.uk/oppf). Involved mainly in an advisory capacity are Structural Medicine, Cambridge (http://www-structmed.cimr.cam.ac.uk) and the Computer Science Department, Cardiff University (http://www.cs.cf.ac.uk/department/staff/o.f.rana.shtml).

Involvement of the SRS in the development of experimental facilities on Diamond (www.diamond.ac.uk)

The Diamond project has the aim of constructing the storage ring and seven experimental beamlines to be operational towards the end of 2006. Further beamlines will be constructed in following years. The work on experimental facilities is co-ordinated by the Diamond Experimental Co-ordination Committee, chaired by Colin Norris with Colin Nave as vice chairman. If Diamond is going to be a success, it will not be enough simply to copy the mechanical design of beamlines built on other 3^{rd generation sources.} It will require a complete systems approach from “source to science” as well as addressing key individual technical areas. One of the aims of the e-htpx grant is to develop systems that will be transferable to Diamond. Other areas include experimental controls and beamline diagnostics/stability which, if properly addressed, will give a competitive edge to the facility.

Development of automatic facilities for protein crystallography data collection. This project has the aim of providing an automatic goniometer together with a sample changer which can change samples at liquid nitrogen temperature. This is a pre-requisite for efficient screening and data collection of the large number of protein crystals resulting from the adoption of high throughput methods. The complete system has to be capable of remote operation and be compatible with the e-science developments above.

Radiation damage and small crystals. It has become apparent that there is a limit to the amount of diffraction data that can be obtained from a single crystal of a protein, even at cryo-temperatures. This results from the action of photo-electrons which are produced when a photon is absorbed. A summary of the latest investigations in this area can be found in a paper by Garman and Nave (http://journals.iucr.org/s/issues/2002/06/00/hi2032/hi2032.pdf ) with more detailed reports from a radiation damage workshop in http://journals.iucr.org/s/issues/2002/06/00/issconts.html . Future work will investigate procedures for collecting data from very small micro-crystals.

This Infrastructure Cooperation Network (ICN) coordinates activities which promote access to research infrastructures required by the macromolecular crystallography (MX) community in Europe. Specifically, it provides a forum for identifying areas of cooperation centred around the exploitation of Synchrotron Radiation (SR) in life science crystallography It brings together large scale facilities, software developers, academic and commercial users and SMEs involved in instrument production to reflect the current requirement of fast throughput structure determination. It organises several teaching workshops every year plus "integration activities" which encourage co-operation among hardware and software developers. One example of such an integration activity is the project to link protein crystallography data acquisition and processing to provide more automatic data collection (see www.dna.ac.uk )