title: Dynamical phase transitions reveal amyloid-like states on protein folding landscapes.
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.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Weber
authors.affiliation: Department of Physics, University of Bath, Bath, United Kingdom.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jack
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Schwantes
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California. Electronic address: pande@stanford.edu.
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D000465:Algorithms; D000682:Amyloid / Q000737:chemistry; D001696:Biomechanical Phenomena; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D044367:Phase Transition; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry
chemical_list: D000682:Amyloid; D011506:Proteins