The Pizza proteins as computationally designed building blocks for biochemical nanostructures.

Recently we have computationally designed self-assembling symmetrical protein building blocks named Pizza. Biophysical characterization has shown that the proteins are very tolerant to truncation, permutation and introduction of multiple mutations. In this project we will combine computational protein design with experimental biochemistry to further develop the Pizza proteins as building blocks for bionanotechnology. Recent preliminary studies demonstrated that derivative proteins can oligomerize upon addition of metal ions and disassemble upon addition of EDTA. As such starting from a single trimeric unit, the protein could assemble into soluble dimeric units, fibers or hydrogel like material (depending on the protein mutant) upon addition of metal ions. In this project proposal we aim the improve the self-assembly of the proteins using computational protein design combined with experimental protein engineering and validation.

To this end we aim to fulfill 4 goals :

1. the design of nanotube forming protein building blocks utilizing Pizza proteins, and evaluation of nanotube formation.
2. the redesign of the Pizza dimer interface for asymmetric orientation specific assembly
3. the combination of the building blocks to form (helical) proteins fibers
4. the combination of the building blocks to form protein hydrogels

Such fibers, tubes and hydrogels assembled from designer proteins with triggered assembly and dissambly have a wide variety of putative applications.