Infrared spectroscopy (IR) based on molecular vibration is a well-established experimental technique and its primary application is to characterize the secondary structural of polypeptides and proteins in the solution as well as in the solid state. Most IR structural dynamic studies focused on H-D exchange of proteins on a global scale. Some studies also focus on the exchange rate of secondary structure components. As a successful and one of the very few demonstrations in structural dynamics, Dong et al. investigated the exchange rate of cAMP receptor protein secondary structural components and facilitated the interpretation of the ligand-induced conformational and structural dynamics changes. Hydrogen deuterium exchange mass spectrometry (HDX/MS) has been widely used to study protein structure, interaction, and dynamics. Most HDX/MS studies utilize a continuous labeling strategy where a native protein is exposed to deuterium oxide (D2O) and the deuterium incorporation is monitored as a function of exposure time. The protein region with open conformations undergoes faster deuterium exchange. Protected or tightly folded regions show slower exchange which is also determined by the dynamic of protein in the solution. This indicates that continuous labeling HDX primarily monitors protein structural dynamic changes, rather than actual structure. However, there is an obvious connection between the two aspects, because tightly folded regions are generally less dynamic than those that are disordered. HDX/MS typically indirectly probe the structural dynamic as a matter of kinetic of deuterium exchange which cannot provide detail of specific motion. As such, HDX was traditionally coupled with NMR analysis to determine protein structure and dynamics at high resolution. 199