All the systems were then gently equilibrated from 10 to 300 K under the NVT ensemble for 50 ps with a weak restraint of 5 kcal mol -1 Å -2 . Subsequently, a density equilibrium was performed using the NPT ensemble at a targeted temperature of 300 K and pressure of 1 atm for 1 ns using the Langevin thermostat and the Berendsen barostat, with a weak restraint of 1 kcal mol -1 Å -2 . Following the removal of all restraints, the systems were further equilibrated for 3 ns, and then 100 ns of production simulations for each system were run and the convergence of the simulation is checked. Furthermore, these procedures were replicated three more times. The covalent bonds that contain hydrogens were constrained using the SHAKE algorithm , and a particle mesh Ewald (PME) method was utilized to treat long-range electrostatic interactions during all the MD simulations. The entire simulation was run with an integration step of 2 fs. The Amber20 package's GPU version was used to run all of the MD simulations.