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The landscape of amyloid misfolding

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If you have a question about this talk, please contact Akhila Kadgathur Jayaram.

Alzheimer’s disease is one of many afflictions that are associated with the formation of beta-sheet rich protein aggregates called amyloids. In this talk I will present a series of analytically tractable toy models to probe the fundamental energy barriers and timescales that determine the kinetics of aggregation. We show that the fast dynamics of secondary structure formation can be mapped to exactly solvable random walks in one and two dimensions to understand the dynamics of fibril nucleation and elongation. While the random walk steps occur on the nanosecond timescale, the theories show that the time to sample the conformational space is consistent with the much longer timescales observed in experiments. These random walk models show that the aggregation process occurs by a very different mechanism than the funnel model that governs native folding.

This talk is part of the Biophysical Seminars series.

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