Incorporating metals into de novo proteins

The de novo design of artificial metalloproteins from first-principles is a powerful strategy with which to establish the minimum structure required for function, as well as to identify the important design features for tuning the chemistry of the coordinated metal ion. Herein we describe recent contributions to this field, covering metallo-porphyrin, mononuclear and multinuclear metal ion sites engineered into de novo proteins. Using miniature artificial scaffolds these examples demonstrate that complex natural protein folds are not required to mimic naturally occurring metal ion sites in proteins. More importantly progress is being made to engineer de novo metalloproteins capable of performing functions not in the repertoire of biology.