Synthetic biology principles for the design of protein with novel structures and functions

Abstract

Nature provides a large number of functional proteins that evolved during billions of years of evolution. The diversity of natural proteins encompasses versatile functions and more than a thousand different folds, which, however, represents only a tiny fraction of all possible folds and polypeptide sequences. Recent advances in the rational design of proteins demonstrate that it is possible to design de novo protein folds unseen in nature. Novel protein topologies have been designed based on similar principles as natural proteins using advanced computational modelling or modular construction principles, such as oligomerization domains. Designed proteins exhibit several interesting features such as extreme stability, designability of 3D topologies and folding pathways. Moreover, designed protein assemblies can implement symmetry similar to the viral capsids, while, on the other hand, single-chain pseudosymmetric designs can address each position independently. Recently, the design is expanding towards the introduction of new functions into designed proteins, and we may soon be able to design molecular machines.

Keywords: coiled coils; de novo protein design; modular design; protein cages; synthetic biology; β-sheets.