IBM has announced the latest project for their World Community Grid distributed computing effort, and it has the potential to be a significant one: a search for molecules that block the reproduction of flaviviruses. That obscure name represents a number of very obvious health issues, as this family of viruses causes dengue fever, yellow fever, hepatitis C, and West Nile disease. The new effort brings together resources from a variety of institutions in the hope of combating these deadly diseases.
The project is being coordinated by the University of Texas Medical Branch, and its home page lists some sobering statistics about the significance of these viruses: two percent of the global population harbors hepatitis C infections, while 1.5 million people annually are treated for dengue fever. Currently, there are no drugs that specifically target any of them.
The Grid hopes to change that. The members of this family of viruses have an unusual structure that presents the opportunity to design therapies that specifically inhibit their infection. In contrast to many other viruses, which have individual genes that encode the proteins needed for their spread, flaviviruses produce a single, large protein that's then chopped up into individual functional parts (a more detailed description is available in this Open Access publication). The virus itself encodes two proteins, called proteases, which help to break the initial protein into the smaller, functional pieces—one of these proteases has now become the target for the World Community Grid.
The Grid's work builds on the determination of the physical structure of the NS3 protease, which has been obtained for both the dengue virus and hepatitis C virus. With the structure in hand, researchers have identified the active site, where the enzyme catalyzes the splitting of the viral protein. The Grid will search for small molecules that fit into the active site in the hope that one of them will block the interaction between the protease and its targets.
That search will leverage ZINC, a free database hosted by the University of California, San Francisco that contains over 4.6 million structures of commercially available chemicals. Individual computers on the Grid, given the protease structure and the structure of a chemical from ZINC, can calculate the energy of association between the two. Two rounds of screening, based on separate pieces of software developed at the Scripps Research Institute and Harvard, will allow researchers to identify the chemicals with the highest specificity of binding to the protease. Those chemicals will then be forwarded to biologists, who will determine how well they protect cells from viral infection.
Overall, the project seems like a great way to contribute to a goal that's a bit more concrete than those of other distributed computing projects. It's also a great demonstration of how essential information sharing is to scientific progress, as the project leverages a combination of data, software, and open information from many individuals and institutions.