We have carried out classical MD simulations using different functional forms of repulsions and found that the softer repulsions make the PMF resemble the shape of the PMF from the quantum-mechanical simulation. In general, the softer repulsive force results in a lower energy barrier between the two potential minima. This indicates that the repulsive part in the Lennard-Jones potential can cause qualitative effects in describing intermolecular interactions. We also compared the forces derived from the density functional theory with the forces used in the classical force-field MD simulation. The floppy nature of molecules should blur the barrier between contact configuration and solvent-separated configuration in the PMF.
Although the softer repulsion creates a lower energy barrier, the barrier between the two potential minima is still more significant in classical simulations than in quantum-mechanical results. From the comparison of Lennard-Jones potentials and interactions calculated by DFT, we find the Lennard-Jones potential is incorrect at short distances, and it has less binding at larger distances as well. The interaction calculated by DFT has a softer repulsion and a stronger attractive force than Lennard-Jones potential until Å. This may be the reason why the PMF calculated by quantum-mechanical simulation differs from the PMF in the classical force-field simulation.
From the variation of the hydrogen-bonded polygon distribution, we found the hydrogen-bond network is sensitive to the size of solutes. The ratio of pentagons to hexagons is larger when the separation is Å, which hints a stable cage structure forms at a specific solute size.