Even with the advances in treating people infected with HIV, there are still about two million new infections and one million HIV-related deaths each year. HIV continues to be a challenge because it quickly mutates in ways that make existing drug treatments ineffective. FightAIDS@Home joined World Community Grid 10 years ago with the simple - but challenging - goal of finding new treatments for HIV. Since then, the project has made some incredible advances in understanding the virus, developing better drug search tools, and identifying chemical compounds that might be able to bind to the virus and disrupt its lifecycle.
The computing power donated by World Community Grid volunteers has allowed the FightAIDS@Home research team to significantly expand their research beyond what they originally planned. Phase 1
of this project is considered to be the biggest docking experiment ever conducted with more than 20 billion drug-target comparisons performed. The research team was able to computationally evaluate millions of chemical compounds against many different regions of the entire viral machinery, rather than restricting the search to only certain compounds or certain binding sites.
Although the researchers expect to run additional Phase 1 screenings in the future, they will now focus on identifying the most valuable results from Phase 1. While the team has already identified thousands of potentially promising candidates to be confirmed experimentally in the lab, it would be cost and time prohibitive to lab test all of the potential candidates. The virtual docking techniques used in Phase 1 are only an approximation of the potential effectiveness of these promising compounds. They can be evaluated in the lab, but this is expensive and slow, because each chemical must be either synthesized or purchased, and then thoroughly tested. Therefore, results from Phase 1 will be filtered to prioritize computationally-selected candidate compounds, evaluating them using more accurate methods in Phase 2.
This is necessary for two related reasons. First, Phase 1 generated a significant number of "false positives," compounds that looked promising in Phase 1 screening but would not actually be effective as HIV drugs. Second, the large number of results is likely to contain other candidates, "false negatives," which scored lower but merit further investigation.
Phase 2 of FightAIDS@Home uses a different simulation method to double-check and further refine the virtual screening results that were generated in Phase 1. The technique is called BEDAM (Binding Energy Distribution Analysis Method), which has proven effective in computational contests, but has been limited to evaluating just a few dozen molecules. It has not yet been used on such a large scale because of the much larger amount of processing time required. With World Community Grid, it will be possible to more thoroughly evaluate the top candidates from the vast number of results generated in Phase 1.
So Phase 2 has two main goals: increase the success rate by reducing false positives and false negatives from the Phase 1 docking data, and prove the BEDAM analysis techniques on a large scale. This should save enormous amounts of time and money in the lab testing stage of drug development.
This new phase is another chapter in a long and well-established collaboration between World Community Grid and The Scripps Research Institute
, a world-renowned research organization. Our teams have already collaborated on other research efforts including the search for treatments against Ebola
. The relationship has been beneficial for all involved. For the researchers, the enormous amount of computing power available through World Community Grid has enabled them to run larger experiments and explore greater numbers of chemicals than they ever thought possible. Furthermore, the virtual screening tools they have developed and refined (AutoDock and AutoDock Vina) are the world's most widely used and cited molecular docking programs and have benefited other World Community Grid research projects searching for drug candidates for other diseases. Once BEDAM is validated on a large scale, it could prove equally useful to these other research efforts as well.
Please continue to support the FightAIDS@Home project as it establishes a new front in the fight against the world's deadliest virus.