Elastic network model- a coarse-grained normal mode analysis- is widely used to investigate the functionally important collective motions of proteins and their complexes. Mixed coarse-graining approach has been recently introduced to the elastic network model, so that the protein's native conformation can be modeled with regions of low and high resolution. In the mixed resolution model, each node of the elastic network may represent either a single atom (high-re solution) or a residue (low-resolution), and close-neighboring nodes are connected by harmonic springs. Here, the high-resolution parts constitute the interesting parts of the protein, such as the active site, while the rest of the structure is retained at lower resolution. By performing normal mode analysis of the resulting network, the collective dynamics (low-frequency modes) and consequent conformational changes can be analyzed even for supramolecular assemblages with reasonable computational efficiency, which may serve as a means of incorporating protein flexibility into docking algorithms and drug design. In this study, the mixed coarse-graining methodology is applied to analyze the functional motions of an important enzyme, triosephosphate isomerase.