TCBG Seminar

Determining the Structural Ensemble of Intrinsically Disordered Disease Peptides combining Theory and Experiment: Applications to Alzheimer’s Disease Biology

Professor Teresa Head-Gordon
Chemistry
University of California @ Berkeley
Berkeley, CA

Monday, November 10, 2014
3:00 pm (CT)
3269 Beckman Institute

Abstract

Intrinsically disordered proteins (IDPs) represent a new frontier in structural biology since their primary characteristic is that structures need to be characterized as diverse ensembles of conformational sub-states. In my talk I will review two general but very different ways for combining NMR spectroscopy with theoretical methods to derive structural ensembles for the disease IDPs amyloid-β 1-40 and amyloid-β 1-42, which are associated with Alzheimer’s Disease. Based on the best experimentally validated theoretical ensemble of the two amyloid peptides, it is now possible to produce a plausible molecular basis for why Aβ42 exhibits greater fibrillization rates than Aβ40. I will also discuss our related theoretical investigations around disease biology questions in Alzheimer’s.


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