tætter på kur mod Alzheimer via folding@home
http://folding.typepad.com/news/2012/03/fah-simulations-lead-to-a-new-t…
taget direkte fra linket:
Drug design studies targeting one of the primary toxic agents in Alzheimer’s disease, soluble oligomers of amyloid ß-protein (Aß), have been complicated by the rapid, heterogeneous aggregation of Aß and the resulting difficulty to structurally characterize the peptide. To address this, we have developed [Nle35, d-
Pro37]Aß42, 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]Aß42 stabilizes the trimer and prevents mature fibril and ß-sheet formation. Further, [Nle35, d-Pro37]Aß42 interacts with WT Aß42 and reduces aggregation levels and fibril formation in mixtures. Using ligand-based drug design based on [Nle35, d-Pro37]Aß42, a lead compound was identified with effects on inhibition similar to the peptide. The ability of [Nle35, d-Pro37]Aß42 and the compound to inhibit the aggregation of Aß42 provides a novel tool to study the structure of Aß oligomers. More broadly, our data demonstrate how molecular dynamics simulation can guide experiment for further research into AD.
taget direkte fra linket:
Drug design studies targeting one of the primary toxic agents in Alzheimer’s disease, soluble oligomers of amyloid ß-protein (Aß), have been complicated by the rapid, heterogeneous aggregation of Aß and the resulting difficulty to structurally characterize the peptide. To address this, we have developed [Nle35, d-
Pro37]Aß42, 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]Aß42 stabilizes the trimer and prevents mature fibril and ß-sheet formation. Further, [Nle35, d-Pro37]Aß42 interacts with WT Aß42 and reduces aggregation levels and fibril formation in mixtures. Using ligand-based drug design based on [Nle35, d-Pro37]Aß42, a lead compound was identified with effects on inhibition similar to the peptide. The ability of [Nle35, d-Pro37]Aß42 and the compound to inhibit the aggregation of Aß42 provides a novel tool to study the structure of Aß oligomers. More broadly, our data demonstrate how molecular dynamics simulation can guide experiment for further research into AD.
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