Metal ions play crucial roles in mediating the structure and function of metalloproteins in biological systems. This review summarized the progress of using rational design of artificial metal-binding sites to expand the functional diversity of proteins, which includes designing artificial metal-binding sites within protein scaffolds by exploring potential metal-binding sites, redesigning existing metal-binding sites, or designing new metal-binding sites, and on the protein surfaces to achieve structural and functional conversions, study interactions with nanomaterials, or perform proteins self-assembly. These progresses greatly enriched our knowledge of the structure-function relationships of metalloproteins, and also endowed us the ability of controlling and utilizing a protein of interest.

Contents
1 Introduction
2 Design of Metal-binding Sites within Protein Scaffolds
2.1 Exploring Potential Metal-binding Sites
2.2 Redesigning Existing Metal-binding Sites
2.3 Designing New Metal-binding Sites
3 Design of Metal-binding Sites on Protein Surfaces
3.1 Structural and Functional Conversions
3.2 Interactions with Nanomaterials
3.3 Proteins Self-assembly
4 Conclusions and Outlook