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Research offers new way to target shape-shifting proteins

The discovery could lead to new methods for identifying drugs to prevent, treat or stop the progression of other conditions in which amyloid fibrils play a role, including Alzheimer's, Parkinson's and diabetes type II.

The research, funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust, is published today (28 August) in Nature Chemical Biology.

The team - from Leeds Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences - found that an antibiotic known as rifamycin SV was able to prevent protein β2microglobulin (ß2m) to form fibrils in . ß2m is known to accumulate in renal dialysis patients and forms fibrils in the joints, causing extreme pain and arthritis.

By using a specialized analysis technique called ion mobility spectrometry and mass spectrometry (IMS-MS), researchers were able to see at what stage of the process of rifamycin SV prevented the formation of amyloid fibrils.They believe the technique could enable drug candidates to identify the proteins that form amyloid fibrils in many other, related to a wide range of human diseases.

"Drug traditional design for diseases such as Alzheimer's is incredibly difficult because the protein you are trying to target the changing shape and structure of all time," said Leeds University, Professor of Structural Molecular Biology, Sheena Radford. "It's like trying to always choose a pearl of a particular form of box potentially millions of similar beads.This new technique allows us to see the shape of the protein as it changes, so we can more easily identify exactly what part we need to target. "

In their normal state and folded proteins can not bind together to form long fibrillar assemblies, but if they occur, they expose the areas where they can bind to each other. Initially, they form small groups of two, three or four proteins, and then those links in long strands, which twist together to form fibrils.

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HPC for biological research | (R news & tutorials)

Although I wrote a post detailing how to use Amazon EC2 cloud for HPC, this workshop has convinced me to use the resources that the NSF is already providing. TeraGrid is a portal that provides access to many resources in the cluster funded by the NSF or any of its partners. Using their portal XSEDE (formerly POPS), scholars can apply for a grant for computing time. For new projects and exploration, there are "seed money", where you can get a fairly generous allocation in a relatively short time. Larger allocations involve a review process.If you currently work time to actively seek funding, the review process is likely to move faster because it has already received a positive opinion. Amazon's compute cluster is still a useful service, but it is not necessary to spend the money elsewhere when NSF grant is already providing these resources. More and more scientists are using TeraGrid resources and to recognize in their publications, which will provide the incentive and justification for organizations such as rDav further research funding, particularly in the fiscal climate of today.

References W.Godsoe, "Regional variations exaggerates differences in patterns of ecological niche." Systematic Biology, vol. 59, 2010.


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