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The WISDOM initiative aims at developing new drugs for neglected and emerging diseases with a particular focus on malaria. Its specificity is to extensively rely on emerging information technologies to provide new tools and environments for drug discovery and development. Its main goal is to boost research and development on neglected diseases by fostering the use of open source information technology for drug discovery. Started in 2005, the initiative has been initially focussing its effort on high throughput virtual screening.
During the summer of 2005, a first large scale deployment allowed achieving in silico docking of 42 million compounds in about 6 weeks against a protein of the parasite responsible for malaria, Plasmodium Falciparum. This success led to a second computing challenge targeting avian flu neuraminidase N1 that took place in April and May 2006.
Results from these two projects are being processed. In the perspective of a fully grid-enabled virtual screening pipeline, the collaboration investigates the reranking of the best hits using molecular dynamics on grid infrastructures.
Looking at the close future, The WISDOM initiative aims at deploying a second data challenge on neglected diseases from October 1st to December 15th on several grid infrastructures including EGEE.
About us
Vision
WISDOM vision is to approach drug discovery from a novel perspective using the most recent Information Technologies. The collaboration is presently aiming at using the grid paradigm to identify potential hits in virtual screening.
Beyond virtual screening, we call for a distributed, internet-based collaboration to address one of the worst plagues of our present world, malaria. The spirit is a non-proprietary peer-production of information-embedding goods. And we propose to use the grid technology to enable such a world wide "open source" like collaboration. The first step towards this vision has been achieved during the summer 2005 on the EGEE grid infrastructure where 42 million ligands were docked for a total amount of 80 CPU years in 6 weeks in the quest for new drugs. Further development of a grid-enabled virtual screening pipeline is underway in several European projects.
Regarding Intellectual Properties issues, potential collaboration partners should accept that all information including analysis of potential hits are made publicly available. If a group takes screening information and synthesizes the physical compound and tests it extensively in the wet-lab, it might establish IP on their side and can establish claims on the physical compound and its behavior in biological assays as long as they cite the source for their initial analysis correctly.
Objectives
WISDOM vision is to approach drug discovery from a novel perspective using the most recent Information Technologies. WISDOM objectives are in line with this vision.
The first objective of the WISDOM project is to develop a full virtual screeening pipeline on the grid. The data challenges presently deployed on the different international grids are focussed on docking but efforts are already under way to extend the virtual screening pipeline to molecular dynamics.
The second objective of the WISDOM project is to develop a knowledge space for research on neglected diseases such as malaria. This knowledge space would allow researchers (biologists, chemists) to access all information relevant to their work in a few mouse clicks.
The third objective is to follow up through the best drug candidates coming out of the data challenges so they are further processed in vitro and in vivo. Our commitment is that our research is useful to find new drugs against such devastating pleas as malaria.
Success stories
WISDOM has achieved deployment of virtual docking at an unprecedented scale on grids. Using the EGEE infrastructure,...
Rationale
Partners
WISDOM is organized with a core group of institutes which are developing the tools used to achieve virtual screening on grids and to make the results as widely available as possible to the research communities. Around this core group of partners, institutes are contributing to the different large scale deployments by committing targets or further studying the best hits coming out of virtual screening. European projects and grid infrastructures are supporting the WISDOM initiative.
We gratefully acknowledge the support of BioSolveIT (http://www.biosolveit.de/).
The following institutes are members of WISDOM core group:
- SCAI, Fraunhofer Institute, Germany (http://www.scai.fraunhofer.de) - LPC Clermont-Ferrand, CNRS-IN2P3 Université Blaise Pascal, France (http://clrwww.in2p3.fr) - University of Modena, Italy (http://www.unimo.it) - ITB-CNR, Italy (http://www.itb.cnr.it) - Academia Sinica (http://www.twgrid.org/) - healthgrid (http://healthgrid.org/)
The following institutes have contributed to the high throughput virtual screening projects already deployed on grid infrastructures:
- Genomics research Center, Academia Sinica, Taiwan (http://www.genomics.sinica.edu.tw) - Pretoria University, South Africa (http://www.up.ac.za) - University of Los Andes, Venezuela (http://www.ula.ve) - ACCAMBA projet, France (http://accamba.imag.fr) - CEA, France (http://www-dsv.cea.fr/content/cea_eng/d_dep/d_drdc) - University of Modena, Italy (http://www.unimo.it)
The following projects support the WISDOM initiative:
- The European project EGEE (http://www.eu-egee.org) - The European project BioinfoGRID (http://www.bioinfogrid.eu) - The European network of excellence Embrace (http://www.embracegrid.info)
The following grid infrastructures have contributed to the world-wide deployments:
- The European EGEE infrastructure(http://www.eu-egee.org) - The Auvergne Auvergrid infrastructure(http://www.auvergrid.fr) - The Taiwan TWGrid infrastructure (http://www.twgrid.org) - The European-Latinamerican EELA infrastructure (http://www.eu-eela.org) - The mediterranean EUMedGRID infrastructure (http://www.eumedgrid.org) - The European-chinese EUChinaGRID infrastructure (http://www.euchinagrid.org)
Acronym
WISDOM stands for World-wide In Silico Docking on Malaria.
The acronyme WISDOM comes from the first screening experiment at a large scale against malaria and is now used as a generic name for the initiative.
Projects
Summer 2005: WISDOM-I
Spring 2006: High throughput virtual screening against avian influenza
Autumn 2006: WISDOM-II
WISDOM-I: Wide In Silico Docking On Malaria
Malaria is a dreadful disease caused by a protozoan parasite, plasmodium. A new strategy to fight malaria investigated within WISDOM aims at the haemoglobin metabolism, which is one of the key metabolic processes for the survival of the parasite. Plasmepsin, the aspartic protease of Plasmodium, is responsible for the initial cleavage of human haemoglobin. The goal was to identify which molecules could dock on the protein active sites in order to inhibit its action and therefore interfere with the molecular processes essential for the pathogen.
WISDOM aims to demonstrate the relevance and the impact of the grid approach to address drug discovery for neglected diseases. This first biomedical data challenge in the EGEE infrastructure is a scalability step through towards a full in silico drug discovery platform.
http://wisdom.eu-egee.fr/malaria/
Partners
LPC Clermont-Ferrand, CNRS-IN2P3 Université Blaise Pascal, France
SCAI, Fraunhofer Institute, Germany
University of Modena, Italy
Press releases
Networking computers to help combat disease (january 2006) http://istresults.cordis.lu/index.cfm/section/news/tpl/article/ID/80155/BrowsingType/Features
Open Day: The Grid and Neglected Diseases (november 2005)
http://public.eu-egee.org/files/WISDOM%20OPEN%20DAY%20FINAL2.pdf
EGEE Battles Malaria With Grid Wisdom (august 2005)
http://public.eu-egee.org/files/battles-malaria-grid-wisdom.pdf
EGEE Speeds Up Hunt for New Malaria Drugs (may 2005)
http://public.eu-egee.org/files/egee-speeds-hunt-for-new-malaria-drugs.pdf http://public.eu-egee.org/files/EGEE-Actu-Malaria.pdf (in french)
First large scale deployment against avian influenza
The H5N1 virus transmission to human has been observed since 1997, but there has been experience of the subtype N1 at least since 1918. However, scientists showed that the N1 and N2 subtypes could evolve into variants under drug stress. Therefore, our initiative is going to study the impact of point mutation on drug resistance. The goal is to screen a large set of compounds against the same target, the influenza A neuraminidase, with various structures predicted from homology methods thanks to grid infrastructure.
http://wisdom.eu-egee.fr/avianflu/
Partners
LPC Clermont-Ferrand, CNRS-IN2P3 Université Blaise Pascal, France
ITB-CNR, Italy
Academia Sinica, Taiwan
Genomics research Center, Academia Sinica, Taiwan
ARDA group (http://lcg.web.cern.ch/LCG/activities/arda/arda.html)
Press releases
EGEE Grid attacks Avian Flu (may 2006)
http://wisdom.eu-egee.fr/avianflu/press/NR_avianfluEGEE.pdf
Grippe aviaire : la recherche sur les nouveaux médicaments gagne du terrain avec la grille de calcul EGEE (may 2006)
http://wisdom.eu-egee.fr/avianflu/press/Communique%20CNRS%20EGEE%20grippe%20aviaire.pdf
http://www.in2p3.fr/presse/communiques/2006/07_egee.htm
L’Auvergne à la pointe de la lutte contre la Grippe Aviaire (may 2006)
http://wisdom.eu-egee.fr/avianflu/press/cpgrippeaviaire.pdf
Networking computers to help combat disease (january 2006)
http://istresults.cordis.lu/index.cfm/section/news/tpl/article/ID/80155/BrowsingType/Features
WISDOM-II: Second Wide In Silico Docking On Malaria
The impact of the first WISDOM computing challenge has significantly raised the interest of the research community on neglected diseases so that several laboratories all around the world have expressed an interest in proposing targets for a second computing challenge. One of the interests for such deployment is the access to high throughput in silico virtual screening thanks to large scale computing resources that majority of life science laboratories can not use, particularly in the research for neglected diseases or in least developed countries. The cost for high throughput experimental screening of millions compounds is estimated to millions euros.
Target overview:
DHFR from P. falciparum - University of Modena: known target of the Chloroquine drug. Chloroquine is now inefficient against drug-resistance parasites due to DHFR mutations.
DHFR from P. vivax - University of Los Andes: Plasmodium Vivax responsible for malaria in South America.
Tubulin from P. falciparum - CEA and Accamba project: new target involved in cell replication, it is a potential target for cancer treatment. Comparative docking of human and P. falciparum tubulins
GST from P. falciparum - University of Pretoria: new target involved in parasite detoxification
Partners
LPC Clermont-Ferrand, CNRS-IN2P3 Université Blaise Pascal, France
SCAI, Fraunhofer Institute, Germany
University of Modena, Italy
Press releases
Not available
Demos
Web site for the WISDOM demonstration during conferences: http://wisdom-demo.healthgrid.org
List of conferences:
HealthGrid 2006 conference, 7-9 June 2006, Valencia, Spain - Best demo award
EGEE'06 conference, 25-29 September 2006, Geneva, Switzerland
