The structures of TMAO, TBA, and H 2 O molecules in the gas phase were optimized using the Gaussian16 quantum chemistry program package. The MP2/aug-cc-pVTZ 28 level of theory was applied to the calculations, and the natural bond orbital (NBO) analysis was performed. The T 1 diagnostic values of TMAO, TBA, and H 2 O molecules were 0.013, 0.010, and 0.010, respectively, confirming that there was no multireference nature. Using the wavefunctions for the optimized molecules, the EFPs were defined by the "MAKEFP" module implemented in the GAMESS-US program package. Before performing the EFP-MD simulations, we evaluated the accuracy of the EFPs. For this purpose, we decomposed the total interaction energies obtained by the quantum chemistry calculations (MP2/aug-cc-pVTZ) into E ES , E EXREP , E POL +E CT , and E DISP through LMO-EDA and compared them with the EFP results. In the LMO-EDA calculations, we applied the counterpoise method to correct the basis set superposition errors. Subsequently, we performed a set of EFP-MD simulations for dilute TMAO or TBA aqueous solutions and pure water. In the EFP-MD simulations, we used a set of cubic periodic boxes with a side length of ~21 Å containing one solute molecule and 300 H 2 O molecules with a canonical (NVT) ensemble and a cutoff distance of 10 Å. The simulation box size was defined to model the dilute aqueous solution (0.18 mmol L - 1 ). In the EFP-MD simulations, we used a time step of 1 fs and a temperature of 298.15 K (defined using a Nosé-Hoover thermostat). Under these conditions, a set of at least 0.8 ns equilibration and 2.5 ns production runs were performed to evaluate the self-diffusion constants, hydrogen-bond dynamics, radial distribution functions (RDFs), and time-dependent intermolecular interaction energies.