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.