Thanks for the update Dr. Morris!

Great information, Dr Morris. Thank you for the update and the link. <dataman>

Hi Garrett,

Thank you for creating this post and for adding that new section to the http://fightAIDSathome.scripps.edu websight.


To the people who responded to this post, you are all very welcome. The members of the FightAIDS@Home team greatly appreciate your interest, your assistance, and your feedback.

Sincerely,
Dr. Alex Perryman


By the way, if you go to:
http://www.scripps.edu/~perryman/CurrentProjects.html
you can view a short mpg movie that displays the dynamics of one of the multi-drug-resistant mutants of HIV protease that we are trying to design drugs against. That is, this movie demonstrates some of the flexibility in the HIV protease target molecule that is being included in the new experiments performed on the FightAIDS@Home grid.

(You can also go to http://fightaidsathome.scripps.edu/team.html , click on my name, and then click on the "Current Projects" link.) The movie can be found by clicking on the link that is at the end of the second paragraph.

Thanks for all the information, mgl_ALPerryman

Knowing what is being done is some of the best encouragement we crunchers can get.

Lawrence

Hi Lawrence and Larry,

You are both very welcome.

At this point, I can't update the pie-charts on the FA@H websight. Garret (Dr. Garrett Morris) is the person who runs that websight, and he is in Italy for a couple weeks. As soon as Garret returns to TSRI, I will ask him about updating those pie-charts.

Your other question requires a much more complicated and careful response:
The research is still too preliminary to present any of those details to the public. In addition, I don't expect to find a full-on protease drug in these current experiments. I expect to find some promising "hits," which means that they are fairly weak binders/weak inhibitors. I have tons of data that I still need to mine and analyze before I will know which compounds are most likely the best "hits." I will then modify, extend, and decorate these different "hit" compounds with different chemical groups (this is called the hit-to-lead optimization phase). After computationally-evaluating the different collections of new compounds that will be produced by modifying these hits, the best-performing potential inhibitors will then be synthesized by collaborators at The Scripps Research Institute, which takes some time. Those synthesized compounds will then be experimentally-analyzed by other collaborators at TSRI and UCSD (as in, they will be analyzed by wet-lab experiments in test tubes and cell cultures), which also takes a lot of time. The results of the wet-lab experiments are then used to help guide the next cycle of computational experiments. It's an iterative, collaborative cycle involving several different labs at both TSRI and UCSD and several different fields/disciplines of science.

As soon as the data is ready to present to the public, I will make sure that you all hear about it, too. And I'll let you know when we start evaluating the potential "leads" on the FightAIDSatHome grid.

Some of the recent experiments have taught us which particular variants of HIV protease to focus on in our current and future experiments, and they taught us how well a compound needs to score before the result should be considered significant. That is, the work done by Max W. Chang, Dr. William Lindstrom, Professor Arthur J. Olson, and Professor Richard K. Belew, which was recently published in the Journal of Chemical Information and Modeling, volume 47, pages 1258-1262 (2007), lets us know which particular multi-drug-resistant mutants of HIV protease should be studied in our current and future experiments.

I'll keep you updated as soon as other promising data is mature enough to be shared with the public.

Thanks for your help,
Dr. Alex Perryman