Peptide-based nanomaterials: Building back better & beyond

The exquisite structure–function correlations observed for native protein filaments have prompted research into the design of simpler peptide-based analogues that can be tailored for specific applications as synthetic filamentous nanomaterials. Sequence-structure correlations that have been established from analysis of native proteins have been previously adapted to create a supramolecular folding code based on simple design principles. While successful, the supramolecular folding code has not been critically examined in terms of the relationship between the proposed models and experimentally determined structures. Recent cryo-EM analyses of peptide-based filaments at near-atomic resolution offers the opportunity to compare the predictions of the supramolecular folding code to the resultant atomic models. The results provide insight into the limitations of the folding code and suggest an approach to refine the design of peptide-based filaments.