The weights of the first PC (Figure , right panel) display that the nonpolarizable force fields relatively well agree which parts of the RIG-I complex contribute most to the different conformations. All non-polarizable force fields display larger magnitude around residue 685 which is part of the long loop (residues 676-720) residing close to the catalytic site (around residue 268 which is mutated in our variant C268F) which normally binds ATP and a Mg ion. The movements of this loop are required to access the catalytic site, and based on these simulations it seems that this loop is fluctuating a lot possibly to accommodate the ATP and Mg binding. The ff19SB+OL3 has higher weight close to residue 439 which is a part of a smaller loop on the other side of the catalytic site. In the OPLS4 force field, higher weights are observed around residue 500 which is a smaller loop region connecting two helices. In all the non-polarizable force fields, the C terminus of the protein gets high weights. The C terminus of RIG-I contains long loop regions without many helical or sheet structures which makes it more structurally unstable than the rest of the protein. Also, it binds the Zn ion which unbinds in many of the simulations leading to more structural instability. This is why the C terminal residues also get high weights in the polarizable force fields which tend to sample more conformations in these less structured regions. The effect of the RNA atoms for the PCA analysis is negilible.