The complexity of designed bionano-scale architectures is rapidly increasing mainly due to the expanding field of DNA-origami technology and accurate protein design approaches. The major advantage offered by polypeptide nanostructures compared with most other polymers resides in their highly programmable complexity. Proteins allow in vivo formation of well-defined structures with a precise spatial arrangement of functional groups, providing extremely versatile nano-scale scaffolds. Extending beyond existing proteins that perform a wide range of functions in biological systems, it became possible in the last few decades to engineer and predict properties of completely novel protein folds, opening the field of protein nanostructure design. This review offers an overview on rational and computational design approaches focusing on the main achievements of novel protein nanostructure design.

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