Similarly to the Ago2 systems, the protein is moving more than the RNA in the simulations (Table ). The RMSD values are slightly higher than with the AGO2 system and lower than with the Cas12j system, indicating that the system remains relatively close to the initial conformation of the crystal structure. The RMSD values observed in the non-polarizable force fields are comparable to each other and AMOEBA simulations displays slightly elevated values. The O3P water model leads to structural integrity issues of the protein, starting from terminals and longer loop regions, similarly to the Cas12j system. This can be easily seen in Figure where the distribution of protein RMSD values in the O3P simulations is very wide, whereas the RMSD in the other simulations remain comparable to the other protein systems. The RIG-I system has both a Zn and a Mg ion which behave differently (Supporting Information Figure ). The Zn ion unbinds from the protein in all the simulations except some of the AMOEBA simulations. The Mg ion is stable, and it stays in its place in all the simulations except for OPLS4.