Success story
Malaria
Last year there were about 350-500 million infections and approximately 1.3 million deaths due to malaria, mainly in the tropics. Malaria is spread by female mosquitoes, which carry protozoan parasites called Plasmodium.
Currently drug discovery seeks compounds that can inhibit or kill invading parasites and infections, but there are potentially millions of candidate compounds. It can take 10 years to discover a drug and another 10 to get it approved.
Grid technology, where the resources of many computers in a network are applied to a single problem at the same time, however, can reduce candidate compounds from millions to thousands or even hundreds, isolating the most promising candidates and speeding up the discovery process.
The idea for malaria came from a conversation I had with a friend, a pastor who works in Burkino-Faso, who told me that malaria is the biggest problem faced by the country,
sayd Dr Vincent Breton, Research Associate at the Corpuscular Physics Laboratory of the French National Centre for Scientific Research (CNRS-IN2P3) in Clermont-Ferrand,
Quite often it's just the developed world that benefits from high-technology like Grid computing. I wanted Grids to benefit Africa.
The new research is particularly important because these diseases are comparatively neglected by large pharmaceutical companies.
Using the FlexX software developed at the Fraunhofer Institute and donated by the BioSolveIT company, WISDOM used the EGEE Grid to match 3-dimensional structures of proteins from the malarial parasite to ligands, chemical compounds that bind to protein receptors.
Grids are particularly well suited to drug discovery because you can compute the probability for one ligand to fit, or dock, to one protein on each computer node in the Grid, giving massive parallelism,
sayd Breton.
But that's not the only way to use Grids in epidemiology. They could also be used to perform epidemiological modelling or federate databases collecting data on infection and treatment in malaria, but also in HIV. This is vitally important information that is currently very difficult to collect in Africa.
Analysis of WISDOM results at the Fraunhofer Institute for Algorithms and Scientific Computing (SCAI) in Germany, joint instigators and participants of the WISDOM project alongside CNRS-IN2P3 in France, allowed the 5,000 most promising compounds out of 1 million candidates to be selected using a relative ranking scale between different ligands. The project identified both known candidates and new ones, which demonstrated the validity of the approach.
This project shows the importance of Grid technology, and the value of a resource like EGEE,
concludes Breton.
Avian influenza
During April and may 2006, a collaboration of Asian and European laboratories has analysed 300,000 possible drug components against the avian flu virus H5N1 using the EGEE, Auvergrid and TWGrid Grid infrastructures. The goal was to find potential compounds that can inhibit the activities of an enzyme on the surface of the influenza virus, the so-called neuraminidase, subtype N1. 2000 computers around the world were used during 4 weeks. Potential drug compounds against avian flu are now being identified and ranked according to the binding energies of the docked models.
With the help of the high-speed computing and huge data managing capabilities of the Grid, possible drug components can be screened and studied very rapidly by the available computer modelling applications,
sayd Ying-Ta Wu, biologist at the Genomics Research Center of the Academia Sinica in Taipei.
This will free up medicinal chemistsâ?? time to better respond to instant, large-scale threats. Moreover, we can concentrate our biological assays in the laboratory on the most promising components, the ones we expect to have the greatest impact.
With these results, the Grid demonstrates that it is a powerful and reliable resource for scientists, opening up new research possibilities and improving existing methods,
said Viviane Reding, European commissioner responsible for Information Society and Media.
I am very grateful to see that the European flagship Grid infrastructure is contributing to solving current and socially important problems such as avian flu.
Taking advantage of the experience acquired in the previous WISDOM data challenge on malaria, the Grid-enabled in silico process was implemented in less than a month on three different grid infrastructures: AuverGrid, EGEE, and TWGrid, paving the way for a virtual drug screening service at a large scale. The majority of computing is conducted on the WISDOM platform; in addition, a light-weight application framework called DIANE was also adopted in this challenge and used to perform a sizeable fraction of the total activity to enable efficient computing resource integration and usage.
This drug discovery application against the avian flu virus was jointly deployed by the Genomics Research Center, Academia Sinica, Taiwan; Academia Sinica Grid Computing Team, Taiwan; Corpuscular Physics Laboratory of Clermont-Ferrand, CNRS/IN2P3, France; Institute for Biomedical Technologies, CNR, Italy, in collaboration with the EGEE project, the AuverGrid regional grid in Auvergne, and the TWGrid. This work took place in collaboration with the EMBRACE network of excellence and the BioInfoGrid project.
