Protein structure is highly dynamic and conformational changes can occur as a result of formulation composition or environmental stress. The native structure of a protein and its storage stability are closely correlated. As such, protein drugs are often formulated as lyophilized solids to preserve their native structure and minimize the rate of degradation during storage. Proteins can undergo conformational changes, denaturation, or aggregation which are all examples of protein dynamics, when formulated and stored under unfavorable conditions. These changes can result in loss of biological activity, reduced solubility, increased susceptibility to degradation, and invoke an immune response. The preservation of the solid-state native structure is crucial for maintaining the stability and functionality of the protein during storage. Understanding protein structure and dynamics is challenging and requires advanced biophysical techniques. Solid-state Fourier transform infrared spectroscopy (ssFTIR), solid-state HDX (ssHDX) and ssNMR are used as some common methods for protein structure characterizations. ssFTIR has been widely used to study the stabilizing effect of excipients on structural changes in lyophilized protein formulation. For example, Allison et al. studied the impact of sugar in inhibition of dehydration-induced lysosome unfolding. The degree of structural protection in FTIR amide I infrared spectra correlated well with the ability of sucrose and trehalose to form the extent of hydrogen bonding between sugar and proteins. In another study, the storage stability of IgG1 and human serum albumin (rHSA) study showed a relatively good correlation with the degree of retention of the native structure of protein during dying from the spectra correlation coefficient of FITR spectra. However, the disturbance of secondary structure does not necessarily correlate to the compromised protein stability. According to several studies, there is a negative association between the degree of retention of native protein structure as determined by FTIR and the propensity of protein aggregation for lyophilized human growth hormone, IgG-1, 203 lactate dehydrogenase, recombinant human albumin, and γ-interferon. Due to its low resolution and semi-quantitative characterization tool for protein secondary structure, it has limited predictive power for protein stability or degradation rates in the solid state. Another limitation is that it only characterizes the global protein conformation changes and cannot monitor the local or tertiary structure changes which also impact the protein stability.