Energy components of aqueous solution: Insight from hybrid QM/MM simulations using a polarizable-solvent model

An energy decomposition method is present in statistical Monte Carlo simulations of aqueous solutions of a series of organic solutes, making use of a hybrid quantum mechanical and polarizable molecular mechanical (QM/MM-PIPF) approach. In the hybrid QM/MM-PIPF method, the mutual solute-solvent polarization effect is specifically considered through a coupled iterative procedure that ensures the convergence of solvent induced dipoles and the solute wave function. It should be noted that the method is an approximate approach without specifically considering the electronic correlation effect between solute and solvent electrons, and energetic results have not been verified by free energy calculations. Nevertheless, the energy decomposition analysis provides insight into the details of the molecular polarization effect. Qualitative trends of the energy components from such analyses provide guidance in the understanding of the nature of intermolecular interactions in biomolecular systems, whereas quantitative results on specific terms may be utilized to derive empirical, yet computationally more efficient, force fields. Polarization effects are found to be significant, which contribute 10% to 23% to the total solute-solvent interaction energies.