Using thousands of computers on an international computing grid, scientists from 27 countries have been searching for the next malaria drug.

Malaria kills more than a million people each year, most of them young children in Africa. To combat the disease, physicists and biologists in 27 countries recently shared their computer resources over a high-speed network. Using an international computing grid, scientists on the WISDOM (World-wide In Silico Docking On Malaria) project analyzed an average of 80,000 possible drug compounds against malaria every hour, looking at more than 140 million compounds altogether.

The computers are all part of EGEE (Enabling Grids for E-sciencE), which brings together computing grids from different countries and disciplines. During the malaria challenge, the project used the equivalent of 420 years of computing power from a single PC. As many as 5,000 computers were used simultaneously, generating a total of 2,000 gigabytes of useful data.

Nearly half of the computing resources came from the United Kingdom, and most of those were from GridPP, a computing grid funded by the Particle Physics and Astronomy Research Council and built to process data from the world's largest particle physics accelerator, due to be turned on later this year in Geneva. Professor Tony Doyle, the GridPP Project Leader, explains, "Although our grid was built to analyze particle physics data, when we have spare capacity we're able to share it with other scientists worldwide. In this case, we're happy to have contributed more than two million hours of computer time to help find drugs against malaria."

Speeding the Search for Malaria Drugs

This phase of the international WISDOM initiative ran between October 1, 2006 and January 31, 2007. Its analysis of possible docking arrangements between drug compounds and target proteins of the malaria parasite will greatly speed up the search for drugs against malaria. WISDOM uses in silico docking, where computers calculate the probability that molecules will dock with a target protein. This lets researchers rule out the vast majority of potential drugs, so they can concentrate on the most promising compounds in laboratory tests. In addition to speeding up the screening process, this reduces the cost of developing new drugs to treat diseases.

"The impact of WISDOM goes much beyond malaria," declared Doman Kim, Director of the Bioindustry and Technology Institute at Jeonnam National University in Korea. "The method developed can be extended to all diseases, and this opens exciting industrial perspectives. Until now, the search for new drugs in the academic sector was done at a relatively small scale, whereas the WISDOM approach allows a systematic inquiry of all the potentially interesting molecules."

This challenge was a consequence of the first, very successful, large-scale in silico docking, which ran on the EGEE Grid in summer 2005. In that case, WISDOM docked over 41 million compounds in just six weeks, the equivalent of 80 years’ work for a single PC. The WISDOM team identified some 5,000 interesting compounds, from which they found three families of molecules that could be effective against the malaria parasite. Laboratories at the University of Modena, CNRS in France and CNR-ITB in Italy are now carrying out more advanced studies of the molecules using molecular dynamics. Following these studies, the enzymology laboratory of the Jeonnam National University in Korea will test them in vitro.

A second computing challenge targeting avian flu in April and May 2006 has significantly raised the interest of the biomedical research community. Laboratories in France, Italy, Venezuela and South Africa proposed targets for the second challenge against neglected diseases. The WISDOM researchers plan a further data challenge on avian flu later in 2007.

The WISDOM project was also supported by BioSolveIT, a German firm that provided more than 6,000 free-floating licenses for its commercial docking program FlexX. "The WISDOM program. Due to the initial success of the data challenge, the company even decided to extend the FlexX license for several weeks, which allowed studying a new target.