A method for probing the mutational landscape of amyloid structure

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A method for probing the mutational landscape of amyloid structure
Motivation: Proteins of all kinds can self-assemble into highly ordered β-sheet aggregates known as amyloid fibrils, important both biologically and clinically. However, the specific molecular structure of a fibril can vary dramatically depending on sequence and environmental conditions, and mutations can drastically alter amyloid function and pathogenicity. Experimental structure determination has proven extremely difficult with only a handful of NMR-based models proposed, suggesting a need for computational methods. Results: We present AmyloidMutants, a statistical mechanics approach for de novo prediction and analysis of wild-type and mutant amyloid structures. Based on the premise of protein mutational landscapes, AmyloidMutants energetically quantifies the effects of sequence mutation on fibril conformation and stability. Tested on non-mutant, full-length amyloid structures with known chemical shift data, AmyloidMutants offers roughly 2-fold improvement in prediction accur...
Charles W. O'Donnell, Jérôme Waldisp&
Added 24 Aug 2011
Updated 24 Aug 2011
Type Journal
Year 2011
Authors Charles W. O'Donnell, Jérôme Waldispühl, Mieszko Lis, Randal Halfmann, Srinivas Devadas, Susan Lindquist, Bonnie Berger
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