Experiments to find out how changes at the molecular level are causing this resistance are difficult and, so far, have not been done. Now, however, Peter Coveney and co-workers from UCL and Queen Mary, University of London have investigated the problem using computer modelling techniques. Their findings are amongst several outputs of the UK e-Science programme that are discussed in a special Theme Issue of Philosophical Transactions of the Royal Society A which is published on 15 August under the title "Large-scale molecular dynamics simulation of native and mutant dihydropteroate synthase-sulfanimide complexes suggests the basis of dihydropteroate synthase drug resistance" by F. Giordanetto, P.W. Fowler, M. Saqi and P.V. Coveney.
They took experimental data gathered from other organisms to build computer models of the sites where drug molecules interact with an organism's protein molecules. They then ran simulations and visualised what happens when a drug molecule approaches each site for both normal and drug-resistant strains of S. pneumoniae.
The simulations and visualisations exploited highly scalable parallel code running on the United Kingdom's national supercomputing facilities. "Without the use of e-Science methods, they would have taken months to perform and quite probably would never have been done. With these new methods, each simulation took just 12 hours", stated Professor Coveney. So far, life scientists have had limited access to and interest in such high performance computing resources; with Grid computing, these resources are becoming more readily accessible.
Professor Coveney and colleagues could see that a very small, but subtle, difference in structure between the normal and drug resistant strains was to blame for the drug resistance. In the normal strain, a drug molecule binds tightly to the site, but in the drug resistant strain it approaches and then drifts slowly away. If the results of the simulation are borne out by experiment, they could point the way to new drugs to combat disease.
e-Science is the very large scale science that can be carried out by pooling access to very large digital data collections, very large scale computing resources and high performance visualisation held at different sites.
The UK e-Science Programme is a co-ordinated GBP 230 million initiative involving all the Research Councils and the Department of Trade and Industry. It has also leveraged industrial investment of GBP 30 million. The Engineering and Physical Sciences Research Council manages the Core e-Science Programme, which is developing generic technologies, on behalf of all the Research Councils.
The UK e-Science Programme as a whole is fostering the development of IT and grid technologies to enable new ways of doing faster, better or different research, with the aim of establishing a sustainable, national e-infrastructure for research and innovation.