Hi Dataman and esoteric17,
You are both very welcome.

I wasn't born in Missouri, either, but I was raised there. I was born in El Cajon (one of the poorest regions of San Diego), but I grew up in a town of about 15,000 people (the 'Burg is its nickname). The old saying is completely true: you can take the boy out of the country, but you can't take the country out of the man.

Since I think it's kind of fun to play "ask a scientist" (and because I believe that it's a duty of scientists to help educate the public), you all can feel free to ask me any general science questions that you have. I can't promise that I will answer it quickly, but if you create a post with a specific question about science, then I will try to answer it. Even if I don't know the answer, I can usually find it fairly quickly.

Thanks again for helping my research,
Dr. Alex Perryman

Dr. Perryman

That is truly a coincidence as I was raised in San Diego (Kensington) and was graduated from UCSD, Revelle College. It is a small world. But that was eons ago as I am retired now.

I hope WCG members will avail themselves of your kind offer to answer questions.

Thanks again, <dataman>

Hello again esoteric17,

You are very welcome.

I am not sure about all of the experiments that Max Chang performed, but from Lindy's notes, I obtained the following info.:

We've used a ZINC-curated form of the NCI library of 262,000 compounds in several experiments. We've used the NCI "Diversity Set" of 1,900 compounds in many experiments. (These compounds have larger structural differences between them than those in the full NCI library; thus, the Diversity Set is supposed to help you explore a larger amount of chemical space in a much shorter amount of time. But you don't cover any particular region of chemical space as thoroughly, since the Diversity Set is much smaller. It's a trade off.) We have also used the ZINC-curated version of the Chembridge database of 566,000 compounds. And we've used the ZINC-curated form of the NCI fragment library of ~ 32,000 compounds. I believe that Max has used a larger library of compounds from the NCI (instead of just using the ZINC-curated form), but I'm not sure.

Lindy prefers the ZINC-curated versions of the NCI libraries, because the ZINC team has formatted and curated the structural files of the compounds from the NCI in very useful ways. When a compound might have several different protonation states or different resonance structures, then all of those different possibilities are included as separate, unique structural files. The ZINC team also removed/filtered out some of the compounds that were too large to have a good chance at becoming small-molecule drugs (that is, they already contained too many atoms, such that extending and decorating them during the optimization process would produce compounds that had a Molecular Weight that was too large to enable the compound to have good kinetic and biodistribution properties.............................according to "Lipinski's rules," which are not always correct for every ligand:target system). The ZINC team also filtered out the compounds that contained weird atom types, which would make them too difficult or too expensive to synthesize. Although the ZINC versions of the NCI libraries contain smaller numbers of compounds, the compounds that they do contain should be more useful during automated, high-throughput virtual screens (that is, they removed some of the potential junk/noise from the full NCI libraries). I haven't really studied these issues myself, yet; thus, I am trying to explain the reasons that Lindy gave to me.

If you know of other potentially-useful libraries of compounds (especially those that we can obtain for free), please let me know. My current expertise is focused more on hit-to-lead optimization than on finding hits by screening large libraries; thus, I definitely have the need and the desire to learn more about these issues (which is yet another reason why I became part of the FA@H team).

Well, we don't have explicit plans to pursue other HIV targets yet, but Prof. Art Olson, Lindy, and I have certainly had a couple discussions about extending FightAIDSatHome to include other AIDS-related targets. Within the next year or two, we'll try to move these ideas from the discussion stage to the planning and the execution stages. But there is still a lot of work that needs to be done on the HIV protease system. I am definitely interested in performing structure-based drug design research against other targets from HIV (especially the multi-drug-resistant mutants of those targets). HIV integrase, HIV reverse transcriptase, HIV gp41, HIV gp120, and the human CCR5 receptor are all worth pursuing. But we first need to assemble a team of collaborators who are interested in synthesizing and testing the potential inhibitors against those specific targets (and who have the time, the personnel, and the funding to do so), before we can really start to develop explicit plans. However, the ideas are certainly floating around. I'll keep you all informed.

Thanks for your help,
Dr. Alex Perryman

Here is a list of 32 Free Chemistry databases with links for each one plus a short description. Hope this helps.

I am from St. Louis, MO currently attending the University of Missouri - Columbia in Columbia, MO.

I joined because I believe it is the least I can do to help people who suffer or will suffer from diseases. And also, distributive computing is very interesting to me.

I would love to find someone smart enough here at Mizzou to network a few Playstation3's together to make a small super computer to help this project out a bit. Its probably wayyyy over my head though technology and money wise.


And also, does anyone have or know where I can get a flyer to put up around my college to promote the World Community Grid?

Thanks,

Ben K.