The Levinthal Problem in Amyloid Aggregation: Sampling of a Flat Reaction Space.

ABSTRACT: The formation of amyloid fibrils has been associated with many neurodegenerative disorders, yet the mechanism of aggregation remains elusive, partly because aggregation time scales are too long to probe with atomistic simulations. A microscopic theory of fibril elongation was recently developed that could recapitulate experimental results with respect to the effects of temperature, denaturants, and protein concentration on fibril growth kinetics (Schmit, J. D. J. Chem. Phys. 2013, 138 (18), 185102). The theory identifies the conformational search over H-bonding states as the slowest step in the aggregation process and suggests that this search can be efficiently modeled as a random walk on a rugged one-dimensional energy landscape. This insight motivated the multiscale computational algori

SUBMITTER: Jia Z 

PROVIDER: S-EPMC5573152 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature