Molecular simulations of metal-coupled protein folding

Many proteins require help from metal cofactors to function properly. Due to the involvement of metal binding, folding of these metalloproteins can be much more complicated. In recent years, several computational methods have been developed to reveal the essential features of metal-coupled protein folding, ranging from quantum mechanics (QM) to atomistic and coarse-grained (CG) simulations. These theoretical tools have achieved great successes in solving the multiscale difficulties arising from metal binding, and provided new insights into the mechanisms of metalloprotein folding. In this review, we first discuss the interaction features of metal-coordination and then introduce several computational models and their applications in metal-coupled folding. Finally we discuss the effects of metal-binding on the protein energy landscape, which is followed by some perspectives.