The chemical accuracy of EFPs was verified for TMAO, TBA, and H 2 O. The EFPs reproduced dipole moments via high-precision ab initio quantum chemical calculations within a 0.14 D error, which is more accurate than that of classical force field models (Table ). The structural parameters of TMAO/TBA-H 2 O dimer models optimized by the EFPs agreed with the MP2 level of quantum chemistry calculation results within 0.14 Å (Figures , and Tables ). The slight difference in dimer formation validates the rigid rotor approximation in the EFP method, at least within our target systems. The total interaction energy and its components, calculated by the EFP method, near the stable conformation of the TMAO/TBA-H 2 O dimer, accurately reproduced the corresponding localized molecular orbital energy decomposition analysis (LMO-EDA) at the MP2 level (Figures ). The mean absolute error (MAE) of the total interaction energy obtained by EFP and MP2 was 1.3 kcal mol -1 . The MAE of each interaction energy component (electrostatic (E ES ), exchange-repulsion (E EXREP ), polarization (E POL ) with charge-transfer (E CT ), and dispersion (E DISP )) was 0.7, 0.6, 1.4, and 0.5 kcal mol -1 , respectively. The H 2 O-H 2 O interaction described by the EFP method has been established previously. The chemical accuracy of the EFP method was thus confirmed.