Bound ions can affect the structure of the protein and the protein-RNA complex. In this study, Ago2 system had a bound Mg ion, Cas12j had a bound Zn ion and RIG-I system had bound Mg and Zn ions. In the Ago2 simulations, the Mg ion stays in place in all the tested force fields (Supporting Information Figure ). In the Cas12j simulations, the Zn ion stays in place in ff14SB+OL3 and AMOEBA force fields, in the other ones it unbinds. In the RIG-I simulations, the Mg ion stays in place in the ff14SB+OL3, ff19SB+OL3 and AMOEBA simulations and unbinds in the others. The Zn ion is fluctuating more, but it displays similar behavior. Based on these results, one should use constraints with the structurally important ions to keep them in place. Due to an error in the preparation process of Cas12j and RIG-I systems for the OPLS4 force field, we did not include the default zero-order bonds to metals. However, this mistake made it possible for us to compare the stability of the ion binding without a bias in these systems.