Identification of Three Interactions to Determine the Conformation Change and to Maintain the Function of Kir2.1 Channel Protein

We find that a conserved mutation residue Glu to residue Asp (E303D), which both have the same polar and charged properties, makes Kir2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kir2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.