Regarding pressure coupling, the Berendsen barostat 39 was used to maintain the pressure constant at 1 bar with a time constant of 1 ps and compressibility of 4.5x10 -5 bar -1 . Isotropic pressure coupling was used for most systems. On the contrary, the crystal simulations were performed in anisotropic boxes, where the pressure of each dimension of the box was decoupled from the other dimensions. In all systems, the temperature was kept constant at 300 K by using the v-rescale algorithm with a time constant of 0.1 ps 40 . The cut-off for electrostatic and van der Waals interactions was set to 1.4 nm and the Verlet update scheme was used for the short range non-bonded interactions with a buffer tolerance of 0.005 kJ mol -1 ps -1 . Long range interactions were calculated with the Reaction Field method for maximum performance during the production phase. The LINCS algorithm was employed for constraining the bond lengths .