FAH data used for patient treatment ??

[White Bear]

Has any of the FAH work data, to date, been used to develop patient treatment drugs or protocols ??

[Jesse_V]

An excellent question! As far as I know, I don't know of any drug on the market today that F@h is directly responsible for. But let me pull up some relevant information:

1) In 2011, Folding@home completed simulations of several mutant forms of amyloid beta, and the paper "Rationally Designed Turn Promoting Mutation in the Amyloid-ß Peptide Sequence Stabilizes Oligomers in Solution" says "Because of the presence of two turns in the mutant peptide which were absent in solid state NMR structures for the fibrils, we propose, fibril formation might be hindered. The biophysical information obtained in this work could aid in the development of structural models for toxic oligomer formation that could facilitate the development of therapeutic approaches to Alzheimer's"

2) Look at the abstract for Paper #58: http://folding.stanford.edu/English/Papers#ntoc38

3) On the Diseases Studied FAQ, it says: "2010 We have been working closely with the Nanomedicine Center for Protein Folding on pushing our lead compounds forward. They have gone from the test tube to the first round of testing beyond that (onto tissue) and we're continuing to refine the compounds based on the results obtained so far. Also, FAH researcher Dr. Yu-Shan Lin has been awarded a BioX Postdoctoral Fellowship for her proposed work on Alzheimer's Disease simulation."

4) In 2010, the Pande lab presented several potential drugs for Alzheimer's, which appear to inhibit the toxicity of one of the proteins behind Alzheimer's: http://folding.typepad.com/news/2008/12 ... ented.html

5) In 2006 and in agreement with experimental data, F@h demonstrated reasonable success in reliably and rapidly identifying specific mutations of p53 that are linked to cancer. Moreover, the study was able to determine the effects of mutations that could not be experimentally measured. This was then followed by further analysis of all possible amino acid possibilities at each position, in order to thoroughly predict cancer-associated mutations, according to the paper "Kinetic Computational Alanine Scanning: Application to p53 Oligomerization"

6) See http://folding.typepad.com/news/2007/09 ... ne-ce.html

7) See http://fah-web.stanford.edu/cgi-bin/fah ... ned?p=7600

8) "The objective of this project is to characterize the dynamics of IL-2. IL-2 is an important component of the immune system. Mutants of this protein are also used to treat diseases like cancer. By better understanding the dynamics of IL-2, we hope to gain insights that will allow us to design other mutants that will serve as even more potent therapeutics. " From: http://fah-web.stanford.edu/cgi-bin/fah ... ed?p=10113

9) "This A3 project for windows and linux clients aims to characterize the dynamics of RNase H, a key component of HIV. By understanding the role of dynamics in its mechanism, we hope to be better able to design drugs to deactivate this enzyme." viewtopic.php?f=66&t=19423&p=193871#p193871

10) In 2006 the Pande lab presented methods for computational drug design which effecitively parallelized those calculations, which increased significantly increased computational efficiency compared to previous techniques and allowed F@h to perform drug design calculations that were otherwise infeasible. Source: Press FAQ and the "Direct calculation of the binding free energies of FKBP ligands using the Fujitsu BioServer massively parallel computer" paper

11) "This project aims to characterize the dynamics of beta-lactamase. Beta-lactamase plays important roles in drug resistance. By understanding the role of dynamics in its mechanism, we hope to be better able to design drugs to deactivate this enzyme." From http://fah-web.stanford.edu/cgi-bin/fah ... ed?p=10115

I think the list could go on, but these are some of what I've found. I mean I don't know of any drug XYZ on the market today that F@h was directly behind. I think it would be much more reasonable to say that F@h performs a lot of the "dirty work" that is difficult to do in simulating a problem, and then someone else takes those results as a foundation for their efforts and so on. Eventually someone will inject some drug into some lab rats, and maybe, just maybe, most of the rats will get better, then maybe tests will be conducted with a small set of humans, and maybe there will be minimal side effects, and then the FDA has to approve the drug, it has to successfully sell, and we'll see it on the market. I haven't yet heard of such a thing following all the way through, at least not in detail. I believe F@h's work is fairly low-level and foundational, but it has great implications all the way up the chain, which is why there's a lot of "this has great potential to go far" mentality among the F@h scientists. In my mind, hitting the lab rat is complete victory, and going all the way through the FDA is a mighty challenge indeed and if accomplished would be undeniably worthy of total celebration. But I believe both of those milestones are exceptionally difficult to get to, and I have no doubt that F@h has made significant progress in getting there, but there's still a lot more work to be done.

[White Bear]

Jesse,

Thanks, for taking the time to generate your detailed response.

It would be interesting to know what happened to, for example:

"4) In 2010, the Pande lab presented several potential drugs for Alzheimer's, which appear to inhibit the toxicity of one of the proteins behind Alzheimer's: http://folding.typepad.com/news/2008/12 ... ented.html ".

[Jesse_V]

Jesse,

Thanks, for taking the time to generate your detailed response.

It would be interesting to know what happened to, for example:

"4) In 2010, the Pande lab presented several potential drugs for Alzheimer's, which appear to inhibit the toxicity of one of the proteins behind Alzheimer's: http://folding.typepad.com/news/2008/12 ... ented.html ".

You're welcome. I'd say that its fairly probable that this #4 ties into the first item on my list. Clearly, further research is required.

[White Bear]

Jessie,

Nice work on your http://en.wikipedia.org/wiki/Folding@home update and revise project.

Thanks, for your efforts.

[Jesse_V]

Jessie,

Nice work on your http://en.wikipedia.org/wiki/Folding@home update and revise project.

Thanks, for your efforts.

Hey you're welcome. It just seemed like it needed to be done and I felt like I could help out a bit. I'm not quite done though! Let me know via PM if there's anything else on the article you feel I should work on.