Abstract

The rational or de novo design of proteins is challenging for a variety of reasons, primarily because we do not fully understand the relationships between protein sequence and structure. However, we must address this if we are to solve the protein-folding problem, and engineer natural or designed proteins with confidence. In addition, exploring rational protein design could uncover hitherto unseen protein structures, and develop functions beyond those offered by natural proteins. In turn, such new structures and functions, as well as the knowledge gained to achieve them, should find applications in protein engineering, bionanotechnology and synthetic biology.

My group takes a modular, synthetic-biology approach to protein design. First, we define small protein modules, make them via peptide and gene synthesis, and characterise them in detail, including by X-ray crystallography. Then, we use the modules as a toolkit to help design and generate more-complex structures, including: barrel-like complexes, which we are exploring as a basis for enzyme and ion-channel design; and supramolecular assemblies, such as nanocages and fibrous biomaterials, which have potential applications in cell biology and regenerative medicine.