Class I major histocompatibility complex (MHC) molecules have three domains, a platform domain and two membrane-proximal immunoglobulin-like domains, an α3 domain and a β₂-immunoglobulin (β₂m). To understand the dynamic interactions among the three domains, we simulated the behavior of a partial model deficient in β₂m and another model deficient in the α3 domain, by normal mode analysis. As a result, the partial model deficient in β₂m was more flexible in interdomain conformation than the other model. The lowest frequency modes (<2 cm⁻¹) observed for the simulations of the partial model deficient in β₂m showed clear interdomain motions as if each domain moved like a rigid body. Such low frequencies and clear interdomain motions were not observed for the simulations of the other model, therefore the interdomain flexibility of the partial model deficient in β₂m may be due to the lowest frequency modes (<2 cm⁻¹). These results suggest that β₂m contributes to maintaining the interdomain conformation of class I MHC molecules more than the α3 domain does, and may offer convincing evidence to support the notion that the α3 domain and β₂m do not have an equal influence on the structural stability of class I MHC molecules.