All MD simulations were performed using the Compute Unified Device Architecture (CUDA) version of particle-mesh Ewald molecular dynamics (PMEMD) in Amber20 37 on graphics processing units (GPUs). The solute molecules were restrained using a potential of 5kcal mol -1 Å 2 and the solvent and ions were subjected to energy minimization (5000 steps) using the steepest descent and conjugate gradient methods. The entire system was then subjected to controlled heating from 0 to 298.15K for 50ps at constant volume using Langevin thermostat with a collision frequency of 1 ps -1 using a canonical ensemble. During the heating process, the non-hydrogen atoms of the solute molecules were restrained using a harmonic potential of 5kcal mol -1 Å 2 . This was followed by another round of energy minimization for 2000 steps using the steepest descent and conjugate gradient methods. The entire system was then subjected to two rounds of equilibration at 298.15K for 50ps using a weak restraint of 0.1kcal mol -1 Å 2 on all the solute atoms in an NPT ensemble. A Berendsen barostat was used to maintain the pressure at 1bar and the SHAKE algorithm was used to constrain the bonds involving hydrogen. A time step of 2fs was used for all MD runs. A production MD run for seven subsystems was performed in an NPT ensemble with a target pressure of 1 bar with a pressure coupling constant of 2ps for each system for 500ns. The data was saved every 50ps.