Effect of β-sheet propensity on peptide aggregation

摘要

The effect of β-sheet propensity on the structural features of peptide aggregates was investigatedusing an off-lattice coarse-grained peptide model. A phase diagram as a function of temperature andβ-sheet propensity reveals a diverse family of supramolecular assemblies. Highly rigid peptides(peptides with high β-sheet propensity) are seen to assemble predominantly into fibrillar structures.Increasing the flexibility of the peptide (reducing β-sheet propensity) leads to a variety of structures,including fibrils, β-barrel structures, and amorphous aggregates. Nonfibrillar entities have beensuggested as primary causative agents in amyloid diseases and our simulations indicate thatmutations that decrease β-sheet propensity will decrease fibril formation and favor the formation ofsuch toxic oligomers. Parallels between β-sheet aggregates and nematic liquid crystals arediscussed.