MD simulations were run with a time step of 2 fs (by making use of the SHAKE algorithm for constraining hydrogen bonds ) and a cut-off 10 Å for non-bonded interactions, while long-range electrostatics were calculated with the particle-mesh Ewald method. Temperature and pressure were controlled by means of the modified Berendsen thermostat (with velocity rescaling 36 of 0.1 ps) and a Parinello-Rahman barostat (with pressure fluctuations at equilibrium every 2 ps). All simulation analyses were carried out using CPPTRAJ and MDAnalysis based on snapshots saved every 50 ps of MD simulation time.