De novo design of protein cages to accommodate metal cofactors

This chapter, by reviewing the papers appeared in the literature in the last 10 years, illustrates the different strategies used for the development of de novo-designed protein cages housing mononuclear and dinuclear metal-binding sites, as well as hemes and metalloporphyrins. This chapter mainly focuses on α-helical coiled-coil and bundle structures, which self-assemble with the metal cofactors. Fewer examples of artificial metalloproteins based on β-sheet structures have appeared in the literature and they are also described in the chapter. The artificial metalloproteins reviewed in the chapter clearly show that de novo protein design provides an attractive approach for the construction of models, which appeared valuable to probe the features required for the function of complex metalloproteins. In this context, the computational procedure may allow to identify the best possible sequence library, rather than the best possible sequence.