Hi Dataman,

Thank you very much! I could always use another coffee mug in my collection. ;)

Cheers,
Dr. Alex Perryman

Hello dango,

You are most welcome.

The timing of the work units is not under my control. But one thing to note is that with these Vina calculations for GO Fight Against Malaria, each work unit involves docking several different ligands against a target. In contrast, the AutoDock work units for FightAIDS@Home each involve docking a fraction of the runs that are needed for docking a single ligand against a target. Vina is super fast!

The naming convention is as follows:
it starts with the abbreviation for the project (GFAM), followed by my internal filename for the target, followed by a unique batch identification number, followed by a work unit identification number. Each batch involves docking 10,000 different compounds with Vina against a single target. The names of the targets start with "x" to indicate that they were superimposed onto a specific, single coordinate reference frame. The x is generally followed by the PDB ID code for the structure of the target being used (see the Protein Data Bank at http://www.rcsb.org/pdb ). NDP refers to the cofactor that is bound to a region of the active site in dihydrofolate reductase (DHFR, the first target for this project). If the target has WATs in the name, then some of the waters from the crystallographic structure of the target were included. In "positive control" docking calculations that involve reproducing the known binding mode of current inhibitors of DHFR, these crystallographic waters can improve the accuracy of the calculations. Other targets have "dry" in the name, to indicate that all of the water molecules from the crystallographic structure of the target were removed. If a compound can displace these crystallographic waters (which we can help determine by docking against both wet and dry versions of the target), then it might receive an extra energetic boost during the binding process. Most of the targets are from Plasmodium falciparum, the species of parasite that causes the deadliest form of malaria, but some of the jobs involve the same type of target from Plasmodium vivax, the species of malaria that causes the most malaria infections (but vivax infections tend to be less fatal than infections with falciparum). Finding new compounds that can inhibit the targets from both Plasmodium falciparum and Plasmodium vivax would be very clinically useful. Some targets have TB in the name, which indicates that these targets are enzymes from Mycobacterium tuberculosis. The three deadliest infectious diseases are HIV, malaria, and tuberculosis. Some of these GO Fight Against Malaria experiments involve screening compounds against the versions of a particular drug target from both malaria and tuberculosis; thus, we'll be sneaking in some tuberculosis research while we fight against malaria. This is scientifically justified, since it is known that some potent inhibitors of dihydrofolate reductase (DHFR) from malaria are also able to inhibit DHFR from tuberculosis. Similarly, some of the inhibitors of malaria's enoyl acyl carrier protein reductase (ENR) are also good inhibitors of the version of ENR from tuberculosis. Consequently, searching for compounds that can inhibit these targets from both malaria and tuberculosis could be very useful against malaria, and it could help advance the research against two of the deadliest infectious diseases on the planet. A few experiments also involve the version of a particular enzyme from humans (such as DHFR). We want to find compounds that are predicted to inhibit the targets from malaria, but we don't want these compounds to strongly inhibit the enzymes in humans (since inhibiting certain human enzymes can cause toxic side effects). Thus, to advance research against malaria, we'll harvest compounds that dock well against the targets from malaria and that also score poorly against the human versions of that enzyme. However, since all data from this project is in the public domain, the data on the compounds that happen to score very well against the human DHFR could help other scientists advance the search for new drugs against some types of cancer or new drugs to prevent the rejection of transplanted organs. I like to design experiments that can produce multiple bangs for the buck. ;)

Thank you very much for your interest and your support,
Dr. Alex Perryman

Hello XSmeagolX,

Thank you very much. But I can't really take credit for that. The badge design was based on the GO Fight Against Malaria logo. This "precious" logo was created by Stefano Forli, Ph.D., one of the other postdoctoral fellows in Professor Art Olson's lab, who is also a member of the GO FAM team.

Thank you very much for your support,
Dr. Alex Perryman

Thank you Dr. Alex Perryman, and all the GO FAM Team, for your amazing dedication and hard work.

P.S. "In bocca al lupo" is indeed "in the mouth of the wolf", but the real meaning is kind of the "break a leg" in english, a way of wishing good luck with a bad thing :)

starting up bringing my 5 cores online to crunch for this as well..

looks like a great project as work progresses i will figure how much i want to push forward on this project but at least to gold badge before i decide how well the project works.

i want every disease cured as soon as possible. cant wait to add this badge to my collection and look forward to progress reports :)