AutoDock helps tackle two AIDS targets, HIV Protease and HIV Integrase
Oxford, UK — 11th March, 2010.
The Scripps Research Institute and the FightAIDS@Home project announce new publications and the discovery of two new anti-HIV compounds.
A recent publication in the Journal of Molecular Biology, on which leading InhibOx scientist Dr. Garrett M. Morris is a co-author, describes a dynamic model of HIV integrase inhibition and drug resistance. This work employed the ligand-protein docking program, AutoDock, of which Garrett is a key developer.
The AutoDock-powered IBM World Community Grid project, FightAIDS@Home, also recently reported the discovery of two fragment-sized compounds by its researchers and others at The Scripps Research Institute, which bind to HIV Protease in a completely novel way, and which may form the basis for a completely new class of AIDS drug. The results are described in this FightAIDS@Home video:
It is estimated that the AIDS pandemic affects more than 33 million people worldwide. The FightAIDS@Home project, which is supported by IBM's World Community Grid, has been performing virtual screening using the ligand-protein docking software, AutoDock, on a variety of wild type and drug-resitant HIV Protease models since 2001, and more recently on a new target, HIV Integrase. The first results against HIV Integrase were just published in the Journal of Molecular Biology (Perryman et al., 2010).
Volunteers in more than 80 countries around the world have downloaded a screensaver that runs AutoDock ubobtrusively in the background, exploiting unused compute cycles. Together, the World Community Grid's volunteers' computers have assembled a supercomputer that ranks in the Top 15 in the world. AutoDock is one of the key ligand-protein docking technologies being developed here at InhibOx.
FightAIDS@Home, the first biomedical non-profit internet distributed computing project, was founded by Prof. Arthur J. Olson and Dr. Garrett M. Morris at The Scripps Research Institute, and Scott Kurowski at Entropia, in La Jolla, California; FightAIDS@Home later joined IBM's World Community Grid. AutoDock has formed the basis for a number of other World Community Grid projects, including the University of Texas Medical Branch's Discovering Dengue Drugs Together and Influenza Antiviral Drug Search in the USA; and Chiba University Cancer Center Research Institute's Help Fight Childhood Cancer in Japan.
Support for the HIV Integrase research, a collaboration between The Scripps Research Institute and Pfizer, was provided by SFP-1758 from the Anti-Virals Research Unit at Pfizer Global Research and Development, Sandwich, Kent, UK. Additional support was provided by the National Biomedical Computational Resource, the National Science Foundation, the National Institutes of Health (American Recovery and Reinvestment Act of 2009, Grant 3P01GM083658-02S1), the Center for Theoretical Biological Physics, and the Howard Hughes Medical Institute. The virtual screening was performed using resources donated by the members of the FightAIDS@Home project, which is part of IBM's World Community Grid.
References
Perryman, A. L., Forli, S., Morris, G. M., Burt, C., Cheng, Y., Palmer, M. J., Whitby, K., McCammon, J. A., Phillips, C., & Olson, A. J. (2010). “A dynamic model of HIV integrase inhibition and drug resistance,” Journal of Molecular Biology, Epub ahead of print, doi:10.1016/j.jmb.2010.01.033.
IBM, World Community Grid (2010). "Two Compounds Discovered that Pave the Way for New Class of AIDS Drug", http://www-03.ibm.com/press/us/en/pressrelease/29568.wss, Accessed March, 2010.
Ono, M., The Scripps Research Institute (2010). "Scientists Find Two Compounds that Lay the Foundation for a New Class of AIDS Drug", http://www.scripps.edu/newsandviews/e_20100208/hiv.html, Accessed March, 2010.