where e -βW (n+m)H 2 O (150-(n+m))H 2 O is the Boltzmann factor of the water solvation work averaging in the canonical ensemble of the system containing 150 -(n + m) water molecules. However, the NCMC move is slightly modified as follows: the calculation of the solvation work W (n+m)H 2 O was performed in two stages, growth and charging. The molecules are grown according to a path of T = 200 segments where each segment t consists in a perturbation of the system by updating the Lennard-Jones parameters followed by relaxation through 200 NVE MD steps: