W. Graham Richards
Department of Chemistry, University of Oxford
Central Chemistry Laboratory
South Parks Road, Oxford OX1 3QH, UK
Computational methods developed in the area of medical imaging can be adapted to find ligand binding sites on proteins. Once the binding site is specified, libraries of real or virtual molecules may be screened to seek out compounds which have very strong affinity. Massively distributed computing enables huge numbers of molecules to be screened.
These approaches will be illustrated by reference to a search for inhibitors of the binding of anthrax lethal factor to the protection antigen. With the site identified some 3.5 billion molecules were tested in 24 days using the power of 1.4 million personal computers running a screen saver. Over 300,000 hits were revealed with approximately 12,000 looking particularly promising.