Nature utilizes metalloproteins to perform chemical transformations with impressive activities and selectivities that can be directly linked to the local environment provided by the protein. A complete understanding of how the protein controls these interactions would allow for the design of functional metalloproteins. The de novo design of proteins with precise control of cofactor and substrate placement has been a challenge in the field, but would allow for the development of customizable, functional metalloproteins.

We can apply our understanding of fundamental (bio)inorganic principles (coordination geometry, ligand type, metal identity, co-substrates, etc.) to build protein scaffolds that not only fold into the desired structure but enforce the metal/metallocofactor binding site. This allows us to build structure-function relationships for natural metalloproteins, but also opens the possibility to apply decades of knowledge from synthetic model systems to produce new-to-nature chemistry.

Some of our guiding questions are: How do proteins tune common metal centers for different activity? How do proteins direct reaction pathways for desired transformations? How do proteins control reaction specificity (chemoselectivity, regioselectivity, etc.)?