The most common polyhistidine tags are formed of six histidine (6xHis tag) residues - which are added at the N-terminus preceded by Methionine or C-terminus before a stop codon, in the coding sequence of the protein of interest. The choice of the end where His-tag is added will depend mainly on the characteristics of the protein and the methods chosen to remove the tag. Some ends are buried inside the protein core and others are important for the protein function or structure. In those cases the choice is limited to the other end. On the other hand, most available exopeptidases can only remove the His-tag from the N-terminus; removing the tag from the C-terminus will require the use of other techniques. It is important to take into account that the computer simulation (by molecular dynamic) will help you to choose between options, for example, whether the His-tag must be digested or engineered to the N- or C-terminal.