Fig. 5: Polypeptides and proteins folding (blue part) and aggregation (green part) combined energy landscape.

The low-energy folded state is separated from the amyloid states by kinetic energy barriers (transition states). In the currently proposed energy landscape25 of fibrillar amyloids crystalline polymorphs occupy the lowest energy minima. Decidedly dissimilar amyloid structures can have similar relative energies, as found for APRTc5b. Therefore, a single aggregation prone sequence may adopt various fundamentally different amyloid topologies (e.g. both parallel and antiparallel). The exact parameters determining the fine structure of the complex amyloid forms remain to be pinpointed.