The interaction mechanism between amino acid residues and carbon dioxide (CO2) in proteins is the theoretical basis of many the most important biological processes in life science, such as photosynthesis in plants and metabolic reaction of gluconeogenesis.The storage of CO2 in proteins is the first step in above important biological processes.The binding interactions between CO2 and amino acid side chains are calculated using MP2/6-311 +G(d,p) method.Possible interaction sites of CO2 in three proteins (phosphoenolpyruvate carboxykinase (PCK), rhodobacter capsulatus, and carbonic anhydrase Ⅱ) are analyzed using MD docking calculations.The NMR spectrums of two pentapeptides (AARAA and AAKAA) are measured in solutions with and without CO2,respectively.The changes of chemical shifts of two pentapeptides are used for analyzing the interactions between CO2 and amino acids.(1) In proteins at least 13 of 20 natural amino acids possess remarkable interaction ability with CO2 molecules.(2) The best binding sites for CO2 molecules are the three alkaline amino acids (cations Arg+, Lys+,and His+).(3) The acidic amino acids (anions Asp-and Glu-) could maintain a suitable pH condition that is necessary for higher concentration of CO2 molecules in solution.Other polar amino acids may provide transferring pathway for CO2 molecules.(4)Histidine plays the role of CO2 molecule deliver, because it frequently changes between protonated form His+ and neutral form His.(5) In most cases the binding interactions between CO2 molecules and amino acid side chains are electrostatic interactions,however, CO2 molecules could form π-π stock interactions with aromatic amino acids (Phe, Tyr, and Trp), also can be packed by hydrophobic amino acids through hydrophobic interactions.