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The TRAPP-Analysis clustering tool was used to extract frames from stable zones and the TRAPP-Pocket tool was utilized to extract frames from unstable zones ( In the case of TRAPP-pocket, numerical descriptors related to the physicochemical properties of the active site were calculated for each frame of the trajectory (Figure 4) in order to identify energetically high conformations, so these conformations were assumed to be energetically unfavorable (Supplementary Figures S7792

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