Minimalist de Novo Design of Protein Catalysts

The field of protein design has grown enormously in the past few decades. In this review, we discuss the minimalist approach to the design of artificial enzymes, in which protein sequences are created with the minimum number of elements for folding and function. This method relies on identifying starting points in catalytically inert scaffolds for active site installation. The progress of the field from the original helical assemblies of the 1980s to the more complex structures of the present day is discussed, highlighting the variety of catalytic reactions which have been achieved using these methods. We outline the strengths and weaknesses of the minimalist approaches, describe representative design cases, and put it in the general context of the de novo design of proteins.