The RNA-protein complex solvated with the Amber protocol was used to start the AMOEBA simulations in OpenMM. To avoid clashes and high energy conformations in this slower force field, we used the last frame of an Amber trajectory as the starting conformation for the Ago2 simulations. The Cas12j and RIG-I simulations were run from the same initial conformation as the other simulations, as we determined no major equilibration issues as with the Ago2 system. The systems were first minimized using Verlet Integrator with 1 ps timestep for a maximum of 100 iterations. The production simulations were run with the default parameters using Langevin integrator, 1/ps collision frequency and 2 fs timestep. We made a preliminary set of 10*10ns simulations of Ago2 system to check for simulation stability, and then conducted a set of 10*100ns simulations for all the systems that were used for the analysis. The simulation frames were saved every 0.02 ns.