Dynamical phase transitions reveal amyloid-like states on protein folding landscapes

J.K. Weber, R.L. Jack, C.R. Schwantes, V.S. Pande

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Developing an understanding of protein misfolding processes presents a crucial challenge for unlocking the mysteries of human disease. In this article, we present our observations of β-sheet-rich misfolded states on a number of protein dynamical landscapes investigated through molecular dynamics simulation and Markov state models. We employ a nonequilibrium statistical mechanical theory to identify the glassy states in a protein's dynamics, and we discuss the nonnative, β-sheet-rich states that play a distinct role in the slowest dynamics within seven protein folding systems. We highlight the fundamental similarity between these states and the amyloid structures responsible for many neurodegenerative diseases, and we discuss potential consequences for mechanisms of protein aggregation and intermolecular amyloid formation.
Original languageEnglish
Pages (from-to)974-982
Number of pages9
JournalBiophysical Journal
Volume107
Issue number4
Early online date19 Aug 2014
DOIs
Publication statusPublished - 19 Aug 2014

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