http://www.worldcommunitygrid.org/forum ... hread=7042
We have updated the Scripps FightAIDS@Home page with the latest pie charts showing our progress so far. We have three! Both Stage 1a and Stage 1b are completed, and all these results are being carefully analysed and archived. Stage 2 is just getting started, and is only 2% completed, as of this posting.
If you are confused about the stages, I'll summarise them here:
Stage 1a:
NCI Diversity Set (1,900) vs. Mutant HIV Protease Panel (270)
Stage 1b:
NCI Set (230,000) vs. Wild Type HIV Protease (1)
Stage 2:
ChemBridge (500,000) vs. Wild Type HIV Protease (1)
Top Hits from Stage 1 vs. Mutant HIV Protease Panel (270)
NCI Diversity Set (1,900) vs. Monomeric HIV Protease (20)
What does all that mean? The part before the "vs." is the set of candidate drug molecules we are screening, which you can think of as differently-shaped keys. The part after the "vs." is the set of HIV protease structures we are trying to fit the candidate drug molecules into, a bit like differently-shaped locks. The numbers in parentheses are the approximate number of molecules in that set. So, Stage 1a involved screening 1,900 different small molecules ('keys') against 270 different forms of HIV Protease ('locks').
In fact, it was Emil Fischer back in 1894 who proposed the idea that enzymes and their substrates have to fit together like a lock and key. Take a look at this nice animation from the University of Nottingham that explains the so-called "lock and key hypothesis" . Fischer won the Nobel Prize in Chemistry in 1902. Of course, molecules aren't rigid bodies like keys, and in the molecular realm things are a little more complicated structurally than familiar keys fitting into locks, but it is a good first approximation.
Our ultimate goal in the FightAIDS@Home project is to find the "pass key" or "master key" that fits not only the most commonly found form of HIV Protease, but also fits the drug-resistant forms of HIV Protease that the virus can evolve over time.
After analysing the results from Stage 1a, we have found one compound that is quite interesting: it binds consistently well to all 270 forms of HIV Protease that we collectively computed against. It is quite a small molecule, and probably would not be specific enough to bind to just HIV Protease, but it could be incorporated into the design of a molecule that would be more specific to HIV Protease.
As we learn more from the results of Stage 1, we will be sure to keep you up-to-date.
Once again, many, many thanks to every single member of World Community Grid who has donated their computers to run FightAIDS@Home?we sincerely appreciate you all.
Dr. Garrett M. Morris
Molecular Graphics Laboratory (Olson Laboratory)
The Scripps Research Institute