EGEE-II INFSO-RI Enabling Grids for E-sciencE WISDOM in EGEE-2, biomed meeting, 2006/04/28 WISDOM : Grid-enabled Virtual High Throughput Screening N. Jacq LPC of Clermont-Ferrand (CNRS/IN2P3) Biomed meeting, Lyon, 2006/04/28

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 2 Partners – Fraunhofer SCAI, Germany (Project PI: Martin Hofmann) – LPC Clermont-Ferrand, France (CNRS/IN2P3) – CMBA, France (Center for Bio-Active Molecules screening) – BioSolveIT – HealthGrid Representing different projects: – EGEE (EU FP6) – Simdat (EU FP6) – AuverGrid (French Regional Grid) – Accamba project (French ACI project) WISDOM : Wide In Silico Docking On Malaria

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 3 High Throughput Virtual Docking Chemical compounds (ZINC): Chembridge – 500,000 Drug like – 500,000 Targets (PDB): Plasmepsin II (1lee, 1lf2, 1lf3) Plasmepsin IV (1ls5) Millions of chemical compounds available in laboratories High Throughput Screening 1-10$/compound, nearly impossible Molecular docking (FlexX, Autodock) ~80 CPU years, 1 TB data Data challenge on EGEE ~6 weeks on ~1700 computers Hits screening using assays performed on living cells Hits refining Using Molecular Dynamics

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 4 Significant numbers Total of 46 million ligands docked in 6 weeks 1TB of data produced Up 1700 computers in 15 countries used simultaneously corresponding to about jobs and 80 CPU years Average crunching factor ~660 Number of running and waiting jobs vs time

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 5 Deployment on EGEE infrastructure, wisdom.eu-egee.fr 10UK1Poland1Germany 1Taiwan2Netherlands9France 7Spain13Italy1Cyprus 2Russia1Israel1Croatia 1Romania3Greece3Bulgaria sitescountrysitescountrysitescountry Countries with nodes contributing to the data challenge WISDOM Total amount of CPU provided by EGEE federation

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 6 Data challenge on avian flu A collaboration of 5 grid projects: Auvergrid, BioinfoGrid, EGEE-II, Embrace, TWGrid Partners Institute : Academia Sinica (Computing Center, Genomics Research Center), CNRS-LPC, CNR- ITB Timescale: –First contacts: March 1st 2006 –kick-off: April 1st 2006 –Duration: ~4 weeks

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 7 Data challenge on avian flu: biological goals The bird flu virus is named H5N1. H5 and N1 correspond to the name of proteins (Hemagglutinins and Neuraminidases) on the virus surface. Neuraminidases play a major role in the virus multiplication Present drugs such as Tamiflu inhibit the action of neuraminidases and stop the virus proliferation The virus keeps mutating and drug-resistant N1 variants can appear The goal of the data challenge is to study in silico the impact of selected point mutations on the efficiency of existing drugs and to find new potential drugs N1H5 Credit: Y-T Wu

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 8 Data challenge on avian flu: grid facts Data challenge parameters: –One docking software: autodock –8 conformations of the target (N1) – selected compounds –100 year CPU to dock all configurations on all compounds Credit: Y-T Wu

Enabling Grids for E-sciencE EGEE-II INFSO-RI WISDOM in EGEE-2, biomed meeting, 2006/04/28 9 Perspectives Future works on the hits : reranking of WISDOM hits by Molecular Dynamics simulations –Approximately 100 CPU years needed –Supported by EGEE-II & BioinfoGrid european projects –Need for ressources on supercomputers (contact with DEISA) –Finally in vitro testing and structure activity relationships Second large scale docking on EGEE in fall 2006 –Several new foreseen targets on malaria, dengue and other neglected diseases. –Resources needed: ~80 CPU years per target –Supported by EGEE-II and EELA european projects, Swiss BioGrid initiative