WISDOM status and perspectives FKPPL workshop March 2010

WISDOM: status and perspectives FKPPL workshop March 2010 – V. Breton

Grid-enabled in silico drug discovery 1 Million drug-like chemical compounds FLEXX/ AUTODOCK Molecular docking 10. 000 drug-like compounds AMBER Molecular dynamics 1000 drug-like compounds Complex visualization Cost for in silico experiment: 100 CPU Years Cost for in vitro tests: 1 -10$ per compound CHIMERA 100 drug-like compounds in vitro tests WET LABORATORY 20% success rate for in vitro tests in vivo tests 2 FKPPL workshop March 2010 – V. Breton

WISDOM 2005 Wisdom-I Malaria Plasmepsin 2006 Data. Challenge Avian Flu Neuraminidase GRIDS EGEE, Auvergrid, Tw. Grid, EELA, Eu. China, Eu. Med. Grid 2007 Wisdom-II Malaria 4 targets 2008 2009 Data. Challenge Diabetes Alpha-amylase, maltase EUROPEAN PROJECTS Embrace EGEE Bio. Info. Grid INSTITUTES SCAI, CNU Academica Sinica of Taiwan ITB, Unimo Univ, , LPC, CMBA CERN-Arda, Healthgrid, KISTI More than 15 papers in peer-reviewed scientific journals 5 patents on molecules 3 FKPPL workshop March 2010 – V. Breton

March 2010: failure of WHISPe. R proposal • Pharmaceutical industry lacks new molecules • WHISPe. R is an in silico drug discovery platform Knowledge Base Learning from in silico experimentation Drug-like Molecules for biological testing New Compound New Target A Priori Knowledge ADAPTIVE WORKFLOW Inside Outside February 10 th 2010 WHISPe. R hearing, Brussels 4

WISDOM activities considerably slowed down in France in 2010 • Lack of funding – WHISPe. R failure • Lack of human resources – Departure of Ana Da Costa, biochemist – Departure of Jean Salzemann, main WISDOM developer in France – New responsibilities for V. B. • However, activities continued in South Korea – See talk from Ms. NGUYEN, Hanh Thi Thanh • Presentations in grid workshops – Interest from several research groups in biochemistry and pharmacology (Congo, South Africa, Vietnam, Israël) FKPPL workshop March 2010 – V. Breton

New opportunities for 2011 • New human resources to develop a virtual screening platform – Ph. D grant from Agence Universitaire de la Francophonie § IFI: Institut de la Francophonie pour l’Informatique § INPC: Institute of Natural Products Chemistry of Vietnam Academy of Sciences and Technologies (VAST) § LPC Clermont-Ferrand – Idea: join efforts with Korean WISDOM partners FKPPL workshop March 2010 – V. Breton

In silico drug discovery Docking compounds coming from biodiversity (CNRS, IFI, INPC, IOIT) PDB database > 50. 000 3 D structures including biological targets for cancer, malaria, AIDS. . . Question: are these products potentially active against cancer, malaria, AIDS ? Hanoï INPC Answer: focussed list of biological targets on which the compound is most active in silico Local Data. Base of Natural chemical products extracted from local biodiversity

Prospects for collaboration in 2011 • Collaborative effort between France, Korea and Vietnam to develop a new virtual screening platform – Technical improvements (KISTI, LPC) § From WISDOM Production Environment to DIRAC (? ) § From AMGA to IRODS § From grid to cloud – Application to drug discovery on SARS and Dengue fever (CNU) – Application to drug discovery from biodiversity (INPC, Vietnam) • Prepare an application to the joint ANR-NSF call for projects FKPPL workshop March 2010 – V. Breton