Wisdom's strategy is based on a virtual screening of molecules with encouraging therapeutic performances: it allows researchers to calculate the probability that a molecule - called an active molecule or "ligand" - will bind to a target protein, thereby altering its biological activity, and, in the case of malaria, the proliferation of the parasite.
Over the ten weeks of the experiment, 4,3 million active molecules or potential medicines were tested, and more than 140 million linkages between these molecules and the target proteins to combat malaria were calculated. Through this process, it was possible to reject a large number of compounds in record time, allowing researchers to focus the biological tests on the most promising chemical compounds. While accelerating the process of selection of the "best" molecules, this strategy can also substantially reduce the cost of developing new medicines against this disease which has an especially large impact on developing countries.
The impact of the approach used in Wisdom goes beyond malaria. This strategy can be extended to all diseases, opening up major possibilities for industry. Furthermore, Wisdom allows for a systematic investigation of all potentially valuable compounds whereas, until now, the search for new medicines in the academic sector was carried out on a small scale.
In 2005, the first large-scale deployment on the EGEE Grid screened more than 41 million chemical compounds in only six weeks, representing the equivalent of 80 years of calculations on a standard computer. Of the 5000 best chemical compounds selected in this screening, three families of molecules in particular caught the attention of the researchers: two were already known for their action on the targeted protein while the third is completely new. Analysis of the most promising compounds is continuing at the University of Modena in Italy and at the Laboratoire de Physique Corpusculaire (LPC) in Clermont-Ferrand, IN2P3/CNRS at the Blaise Pascal University before being sent for in vitro tests at the enzymology laboratory of Chonnam National University in South Korea.
The success of this first initiative attracted the interest of the international research community, which led to a deployment for avian influenza in April and May 2006 and then this second deployment for malaria for new target proteins proposed by French, Italian, Venezuelan and South African laboratories. Many calculation Grids joined this effort: the regional Grid AuverGrid in Auvergne, the EELA, EUChinaGRID, EUMedGRID and ASGC TWGrid Grids made their calculation resources available, supplementing those of the EGEE Grid. Lastly, two other European projects, Embrace and BioinfoGRID, are contributing to improving the selection of the most promising molecules from among the millions of commercially-available chemical compounds.
For this second phase of the Wisdom project, more than 5000 computers were mobilized simultaneously in 27 countries, producing more than 2000 gigabits of data, which represents the equivalent of 413 years of calculations on a single computer. In France, several CNRS laboratories made a very significant contribution: the Calculation Center of IN2P3 manages the resources made available for this initiative and the LPC supervises the use of the resources for the various scientific calculations. The contribution of all of the French laboratories on the EGEE Grid represents about 15 percent of the 413 years of calculations.