As organic compounds containing an alkaline amino group and acidic carboxyl group, an amino acid is the basic unit of protein, whose type, quantity and arrangement directly affect the biological function of protein with great significance to maintain the body function. Most amino acid intermolecular vibrational modes (torsion, hydrogen bonding and collective vibrations) occur in the THz band and exhibit unique absorption characteristics. Consequently, THz spectroscopic studies of amino acids can give a more comprehensive understanding of biological properties. It was a summary of the absorption spectra of leucine and isoleucine located in the 0. 2~2. 6 THz band measured by previous authors, and, at the same time, the formation mechanism was explained using quantum chemical calculations. Using Gaussian09 software for single-molecule configuration simulations, the simulations were performed by semi-empirical method (PM6), ab initio method (HF, MP2) and density functional theory (B3LYP, M06-2X) combined with 6-311+G(d,p) Gaussian basis groups. Materials Studio 2019 software was used to calculate the cell configuration simulations for four density generalized gradient approximations such as PBE, PBEsol, RPBE and WC combined with plane wave basis groups. The results indicated that the single-molecule configuration simulations lacked absorption peak positions, and the peak positions were calculated differently for the same vibrational mode by different methods. So, for structures with strong intermolecular interactions, the simulation of this configuration by a single method did not correctly match the vibrational modes to a large extent and was influenced by the linear combination of atomic orbitals method. Compared to the input structure, the output structure changed from COO- and NH+3 groups to COOH and NH2, which did not reflect the actual vibrational mode. The intra and intermolecular vibrational modes were described by the cell configuration simulation. The absorption peak positions matched well with the measured values without proton transfer. The vibrational modes of the measured peak positions were better identified. The closest results of leucine and isoleucine calculations using the PBEsol general function to the measured values indicated that full consideration needs to be given to the matching of structure and general function in the simulation, i. e. , the description of the structure exchange association energy and showed the universality of the same general function for the isomers. In addition, the difference after structural optimization cannot be used as the criterion to judge functional applicability. The results of cell configuration calculation include the intermolecular vibration mode, which cannot be obtained with a single molecular configuration. Moreover, the full width at half maximum fitting leads to the difference in the vibration mode of the two configuration results at a measured peak position.