On the entropic driving force of the contact-minimum configuration of two large Lennard-Jones particles in TIP4P/2005 water

In a recent work by Naito, Sumi, and Koga (NSK) [Naito et al., J. Chem. Phys. 161, 214501 (2024)], the analysis of long molecular dynamics (MD) trajectories showed that the formation of the contact-minimum (cm) configuration of two Lennard-Jones (LJ) particles in the TIP4P/2005 water model is driven by entropy, regardless of the particle diameter. This result is striking as it contrasts with the claim that the driving force should be enthalpic for large spherical particles. The observed entropy gain must arise from water, and its molecular origin needs to be clarified. In the past, one of us [Graziano, Chem. Phys. Lett., 499, 79 (2010)] devised a theoretical approach based on the geometric features of the cm configuration. The latter has a smaller solvent-excluded volume than the two particles when they are separated by a large distance. The decrease in solvent-excluded volume, which can be measured by the decrease in water accessible surface area, produces an increase in the volume available to water molecules, which translates into an increase in their translational entropy. This entropy gain drives the formation of the cm configuration. Applying this geometric approach to the largest LJ particles investigated by NSK yields values for the water-mediated thermodynamic functions consistent with those obtained through MD simulations.