Mission and description of GO Fight Against Malaria
On November 16, 2011, we launched our new Global Online Fight Against Malaria project on IBM's World Community Grid. For a brief description of the project, check out this two minute YouTube clip:
For a thorough summary of phase 1 of the project and of the progress we have made so far, please read the new project update, posted July 14, 2014.
For a new paper that we published on January 30, 2015, about the results from GO FAM experiment 5 that could lead to new directions in tuberculosis research, click here and check out the animation at the bottom of this page.
Malaria is one of the three deadliest infectious diseases on earth. Half of the entire human population is at risk of being infected with malaria. Plasmodium falciparum, the parasite that causes the deadliest form of malaria, has killed more people than any other parasite on the planet. In 2006, 247 million people became infected with malaria. New data indicate that over a million people die from this disease each year, and over half of them are children. In fact, it's the leading cause of death in Africa for those under age five. Every 30 seconds, another child dies of malaria. According to the World Health Organization, malaria is both a disease of poverty and a cause of poverty. The survivors of malaria infections are often subjected to impaired learning, other developmental disorders, school absences, lost work, and increased economic distress. Where it's prevalent, this disease can account for 40 percent of all public health costs.
The GO Fight Against Malaria project is part of Professor Art Olson's lab at The Scripps Research Institute in La Jolla, CA, U.S.A. We are performing this project on World Community Grid in order to discover promising candidate compounds that can be developed into new drugs that cure drug-resistant strains of malaria. In this project we will computationally evaluate millions of chemical compounds against different molecular drug targets from the malaria parasite. These computations will estimate the ability of the chemical compounds to disable the particular proteins that the Plasmodium parasite needs to survive, multiply, and infect humans. That is, these "docking calculations" predict whether a particular compound can bind to and disable key components of the molecular machinery that the malaria parasite needs to survive and reproduce. Data from these GO Fight Against Malaria experiments (and data from all World Community Grid projects) are available to the public. If any scientists from around the world want a copy of the GO FAM results, all they have to do is ask. How cool is that! After we process, measure, sort, and visually examine these computational results, the best-ranked candidate compounds will then be evaluated in test tubes and Petri dishes by collaborators (scientists in other labs), to see how effective they are at killing this parasite. When we discover promising compounds that are proven to disable key proteins from the malaria parasite, we will publish these results and share them with the global community of malaria researchers. We and other scientists will then be able to build upon these results and try to develop these promising compounds into new drugs that can kill the multi-drug-resistant superbugs that cause this deadly infectious disease. Please donate your unused computer power, and let your PCs work on the problems that plague humanity. Please join World Community Grid and help us and other labs advance the research against several diseases! As Frank Sinatra sang, "it's nice work if you can get it, and you can get it if you try!"
Because of the power of World Community Grid, what we accomplished with one year of the GO Fight Against Malaria project could have taken us well over one hundred years to achieve, using the resources we normally have available.
In just 19 months, over 27,385 CPU years of computer time were donated to the Global Online Fight Against Malaria! We have performed over 1.16 billion different docking jobs for the GO FAM project!! Your donated computer time enabled us to have the first academic research project to ever perform over a billion docking jobs. The members of the GO FAM team at TSRI and at Rutgers University-NJ Medical School are very grateful for all of your interest and generous support!!!
We have started analyzing, testing, and extending the results that this Global Online Fight Against Malaria project generated, and we look forward to sharing with you the insights that we will gain from these calculations. As this project progresses, we will keep you informed about the details of the experiments we are performing, the progress achieved, and the results that we publish. As you may know from our experience with the FightAIDS@Home project ( http://fightaidsathome.scripps.edu ), we will do our best to keep you informed and up-to-date by posting to the World Community Grid Forum for the GO FAM project and by responding to the questions and comments that you write there.
GO FAM experiment 5 included docking calculations against a key drug target for curing tuberculosis called "InhA," which is shown as lavender ribbons. The most potent new compound we discovered is a small, "fragment-sized" molecule--its predicted binding mode is displayed as thick sticks with cyan carbon atoms. The parts of InhA with which this compound is predicted to form the strongest binding interactions are shown as thin, dark purple sticks. Since this compound can block the activity of InhA without requiring prior activation (processing) of it by the enzyme "KatG" from Mycobacterium tuberculosis (Mtb), it might enable the future development of larger, more potent compounds that can defeat some of the drug-resistant mutant "superbugs" of Mtb (the bacteria that causes TB). See our new paper here and learn more here.
Click on the links in the menu in the top-left corner to learn more about malaria, about who we are, and about how you can help us fight this deadly infectious disease. And check out the images below, which are from "positive control" calculations that prove that we can accurately predict/reproduce the detailed "binding mode" that some known, current inhibitors use to interact with and disable some key protein targets from the malaria parasite.
The two images below compare the experimentally-determined, X-ray crystallographic binding mode of WR-99210 (in purple), a potent inhibitor of dihydrofolate reductase from Plasmodium falciparum (Pf DHFR), to the mode that we predicted with the new software "AutoDock Vina" (in cyan). Although this inhibitor can bind to and disable the multi-drug-resistant quadruple mutant superbug version of Pf DHFR, this compound is not "orally bioavailable" (that is, its chemical properties mean that it can never be turned into a pill, which is why we need to find other new inhibitors of this drug target).
For Frequently Asked Questions, see the FAQs page at:
This GO FAM website was created by Alex L. Perryman, Ph.D., now a Research Teaching Specialist III in Prof. Joel S. Freundlich's lab at Rutgers University-NJ Medical School. It was last modified on 2/06/2015 by Dr. Alex L. Perryman. All of the molecular images were created by Dr. Perryman using PMV (the "Python Molecular Viewer") 1.5.6 release candidate 3.