Missing hydrogen atoms and an appropriate number of counterions to neutralize the complexes were added by the Leap module of Amber20. Thereafter, each complex was immersed into a truncated octahedral box of TIP3P water molecules with the boundary of the protein system being 15Å away from the box edges. The periodic boundary conditions were employed in all the simulations. Long-range electrostatic interactions were calculated using the particle mesh Ewald (PME) with a cut-off of 12Å for the direct space Coulomb and van der Waals forces.