According to the structural studies, the direct Cdc37 binding with the lid motif inhibits the formation of the closed lid conformation and triggers arrest of the Hsp90-ATPase cycle in the open Hsp90 conformation. For the Hsp90-Cdc37 complex, the employed coarse-grained modeling approaches also converged to a consistent dynamics profile of the lid motif demonstrating that structural immobilization of the lid is the fundamental dynamic feature of the Hsp90-Cdc37 binding. In agreement with the experimental data, functional dynamics maps captured a more subtle effect by observing that the boundaries of the structurally stable core could be extended towards L29, A55, and L103 residues from the first, second, and fifth a-helices of the Hsp90-NTD. The Cdc37 interfacial residues M164, L165, R166, R167, and L205 that displayed a strong decrease in signal intensity in the NMR experiments were also structurally stable in the dynamics analysis. The force constant profile of the Hsp90-Cdc37 complex is marked by a steep hike for the lid residues reflecting a significant increase in structural rigidity. Interestingly, the top 10% of high force constant residues in the Hsp90-Cdc37 complex include G132, Q133, V136, G137, and F138 residues from the lid motif. Structural rigidity of the lid in Hsp90-Cdc37 complex determines the position of I110 and F138 hinge sites, clearly demarcating the borders separating structurally rigid core within the Hsp90-Cdc37 complex. Hence, from a dynamic perspective, the primary inhibitory role of Cdc37 in arresting ATPase cycle may be AbMole Ascomycin fulfilled by switching conformationally mobile lid into “rigid” open position via local interactions and AbMole Ellipticine without invoking substantial allosteric changes. This mechanism is another manifestation of cochaperonebased manipulation of the lid dynamics. It is radically different from the Rar1-mediated mechanism that promotes the enhanced conformational mobility of the lid and effectively destabilizes both the fully open and fully closed lid forms. Hence, coarse-grained dynamics analysis has identified common and distinctive dynamic signatures of the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes as compared to the Hsp90-Cdc37 binding. Consistent with the experimental evidence, our results suggested that targeted modulation of the lid dynamics as a common characteristic of the client recruiter cochaperones. In summary, we provided a quantitative characterization of the functional dynamics in the Hsp90-cochaperone complexes that suggested a linkage between cochaperone-induced modifications of the lid dynamics and global structural changes that could enhance the ATPase activity. In the next section, we analyze networking characteristics of the Hsp90-cochaperone interactions to understand how targeted modulation of the chaperone dynamics is allosterically coupled with specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of diverse client proteins. These network parameters can characterize densely packed and structurally stable regions, thus providing a simple yet robust metric for evaluation of structural stability in the protein structures. In the network analysis, communities were identified using both the interaction residue connectivity and cross-correlation contact maps obtained from the ENM-based normal mode analysis. We focused on the network analysis of the regulatory Hsp90-Sgt1-Rar1 complex by placing a specific emphasis on the distribution of the interfacial cliques, communities and hubs. It is evident that the Rar1-CHORD2 interactions in the ternary complex are central to the formation of the interaction network, producing a considerable number of interfacial communities.