Effect of β-sheet propensity on peptide aggregation

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