Next, we analyzed the interaction between the CH 3 -group and the surrounding water molecules (r < 3.5 Å) in a TMAO/TBA solution. In this instance, the difference in the solute does not cause any difference in the charge-transfer and dispersion interactions. This can be explained by the small overlap between the proton donor orbitals of the CH 3 -groups of TMAO/TBA and the molecular orbitals of water (Figures S9, S10, Table ). However, the polarization interaction energy of TMAO is more than twice that of TBA. The large dipole moment of TMAO in an aqueous solution affects even the CH 3 -group. Assuming that the polarization interaction was zero, the interaction between the CH 3 -group of TMAO and water would stabilize at -0.8 kcal mol -1 because of the contribution of the dispersion interaction, which is similar to that of TBA, and a hydrophobic interaction would be induced. In conclusion, the attractive interactions near the CH 3 -group of TMAO are characterized by polarization interactions.