From Implicit to Explicit: An Interaction-Reorganization Approach to Molecular Solvation Energy

Accurate calculation of solvation energies has long fascinated researchers, but complex interactions within bulk water molecules pose significant challenges. Currently, molecular solvation energy calculations are mostly based on implicit solvent approximations in which the solvent molecules are treated as continuum dielectric media. However, the implicit solvent approach is not ideal because it lacks certain real solvation effects, such as that of the first solvation shell, etc. Here, we propose an explicit solvent approach, interaction-reorganization solvation (IRS) method, for molecular solvation energy calculations. The IRS approach achieves predictive accuracy comparable to that of the widely recognized solvation model based on the density (SMD) method and is significantly more accurate than that of the Poisson–Boltzmann/generalized Born surface area (PB/GBSA) methods. This is demonstrated in both the correlation coefficient and the mean absolute error (MAE) with respect to the experimental data. The IRS method is based on molecular dynamics simulation in explicit solvent and does not need to solve Poisson–Boltzmann or Schrödinger equations. On the other hand, the accuracy of the IRS method does depend on the accuracy of the molecular force field used in MD simulations. We expect that the IRS method will be very useful for the solvation energy calculations of molecules.