The Ago2 complex was solvated with truncated octahedron water box with 15Å buffer using 0.15M NaCl solution with SPCE water model. The simulations in Desmond consisted of the default minimization and relaxation protocol and the production run applying Desmond default parameters as well: 2 fs timestep, ensemble class NPT with temperature 300 K controlled by Nose-Hoover chain thermostat and pressure 1.01325 bar maintained by Martyna-Tobias-Klein barostat, recording interval was set to 100 ps. The Desmond simulations of Ago2 complex were 8*250 ns in length, resulting in 2 μs of total simulation time. The smaller Cas12j and RIG-I complexes were placed in the cubic box with 12 Å buffer and solvated using 0.15M NaCl solution and SPCE water model. Both complexes were initially prepared with Protein Preparation Wizard and then processed with pdb4amber to preserve the naming of the atoms, which was important for the further cpptraj analysis. The Cas12j and RIG-I structures obtained in the following way were solvated and used for the Desmond simulations. However, due to absence of additional Protein Preparation Wizard step after using pdb4amber script, zero-order bonds to metals (Zn and Mg) were omitted, and therefore the movements of these ions were unconstrained during simulation of Cas12j and RIG-I complexes in OPLS4 force field. After default minimization and relaxation protocol, the production run was parametrized using default settings with the temperature and pressure changed to comply with Amber simulations: NPT ensemble class, temperature 310 K, pressure 1.0 bar and recording interval each 100 ps. The Desmond simulations of the Cas12j and RIG-I complexes were run in 4*500 ns replicas, total 2 μs of simulation time.