The simulation systems were set up by placing the protein complex in a cubic periodic boundary box with edge length of 140 Å. The systems were first neutralised by adding Na + ions as counterions then solvated by adding water molecules (TIP3P water model 45 ). To simulate physiological conditions, water molecules were replaced by ions at random to achieve a concentration of around 0.15 M NaCl. Each system underwent a 5-stage minimisation, heating, and equilibration process before production runs: