FAH simulations lead to a new therapeutic strategy for AB

[beer]

http://folding.typepad.com/news/2012/03 ... sease.html
taken direct from the link
Drug design studies targeting one of the primary toxic agents in Alzheimer’s disease, soluble oligomers of amyloid β-protein (Aβ), have been complicated by the rapid, heterogeneous aggregation of Aβ and the resulting difficulty to structurally characterize the peptide. To address this, we have developed [Nle35, d-
Pro37]Aβ42, a substituted peptide inspired from molecular dynamics simulations which forms structures stable enough to be analyzed by NMR. We report herein that [Nle35, d-Pro37]Aβ42 stabilizes the trimer and prevents mature fibril and β-sheet formation. Further, [Nle35, d-Pro37]Aβ42 interacts with WT Aβ42 and reduces aggregation levels and fibril formation in mixtures. Using ligand-based drug design based on [Nle35, d-Pro37]Aβ42, a lead compound was identified with effects on inhibition similar to the peptide. The ability of [Nle35, d-Pro37]Aβ42 and the compound to inhibit the aggregation of Aβ42 provides a novel tool to study the structure of Aβ oligomers. More broadly, our data demonstrate how molecular dynamics simulation can guide experiment for further research into AD.

[Jonazz]

We've never been this close to actual drugs.This proves that FAH simulations are accurate and can prove to be a good way to battle diseases in the future. Great news!

[Jesse_V]

That is truly fantastic. But I'm a bit confused, because at the bottom of the publication it says "We acknowledge the UCLA Jim Easton Consortium Alzheimer’s Drug Discovery and Biomarker Development, the NIH Nanomedicine Center (PN1 EY016525), and the Stanford Center for Molecular Analysis and Design (CMAD) for funding. We also acknowledge NSF award CNS-0619926 and no. 0960306 (MRI-R2: Acquisition of a Hybrid CPU/GPU and Visualization Cluster for Multidisciplinary Studies in Transport Physics with Uncertainty Quantification) for computing resources." Normally they say something like "We thank Folding@home volunteers worldwide for their computational resources" and maybe they're under no obligation to say such a thing, but the term "Folding@home" is not found within the article, nor is "distributed", and the term "worldwide" is not used in a computing context. Thus, while a significant accomplishment nonetheless and I'm certainly impressed, I'm not sure that Folding@home actually provided the computing resources for this particular publication. That being said, the work does test predictions that were made using Folding@home. I guess they use whatever resources that they deem most effective for a particular task, which isn't always Folding@home, but I just wanted to point some things out. I've heard Dr. Pande describe FAH as a rocket, which once started goes really far. Perhaps they didn't need such power for this particular work.

[VijayPande]

Here, the predictions were made using FAH several years ago (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674793/) and we're now showing experimentally that those FAH results actually can lead to new small molecule drug candidates. There are a lot of experiments in this latest paper testing FAH's predictions, but not any new FAH simulations.

[VijayPande]

PS I've been wanting to talk about these results for a while but it took a long time to get the experiments completed and get the paper out. As always, it's the latest stuff in the lab (i.e. the next steps from what's published) that's always the most exciting parts. I'm looking forward to tell you all about what's going on now once we're further along. We are pushing hard towards what could be a drug for AD.