  Polypeptides can self-assemble into hierarchically organized fibrils
consisting of a stack of individually folded polypeptides driven together by
hydrophobic interaction. Using a coarse grained model, we systematically
studied this self-assembly as a function of temperature and hydrophobicity of
the residues on the outside of the building block. We find the self-assembly
can occur via two different pathways - a random aggregation-folding route, and
a templated-folding process - thus indicating a strong coupling between folding
and assembly. The simulation results can explain experimental evidence that
assembly through stacking of folded building blocks is rarely observed, at the
experimental concentrations. The model thus provides a generic picture of
hierarchical fibril formation.
