Solvation Free Energy Calculation Using a Fixed-Charge Model: Implicit and Explicit Treatments of the Polarization Effect.

In this work, IPolQ-Mod charges and the reference potential scheme are used to calculate the solvation free energies of a set of organic molecules. Both methods could capture the phase transfer of a solute with accompanying polarization cost utilizing a fixed-charge model. The IPolQ-Mod charges, which are the average of two charge sets fitted in a vacuum state and a condensed phase, take account of the polarization effect implicitly. For the reference potential method, the quantum mechanics polarization corrections are calculated explicitly by thermodynamic perturbation. The polarization effect captured by the IPolQ-Mod charges is an approximation to that of the reference potential method theoretically. In the present study, the reference potential method shows a slight improvement over the classical restrained electrostatic potential (RESP) charges, which perform pretty well in predicting the solvation free energy. However, IPolQ-Mod(MP2) shows a poor agreement with the experimental data. Compared with IPolQ-Mod(MP2), IPolQ-Mod(M06-2X) or IPolQ-Mod(ωB97X) is found to give more appropriate prediction of the molecule's dipole and the solvation free energies calculated by IPolQ-Mod(M06-2X) or IPolQ-Mod(ωB97X) are more compatible with those of the RESP charges. If the other force field parameters remain unchanged, M06-2X or ωB97X is recommended to derive the IPolQ-Mod charges.