The heat shock protein (HSP90) has been an import target of drug design in the treatment of human disease. An exploration of the conformational changes in HSP90 can provide useful information for the development of efficient inhibitors targeting HSP90. In this work, multiple independent all-atom molecular dynamics (AAMD) simulations followed by calculations of the molecular mechanics generalized Born surface area (MM-GBSA) were performed to explore the binding mechanism of three inhibitors (W8Y, W8V, and W8S) to HSP90. The dynamics analyses verified that the presence of inhibitors impacts the structural flexibility, correlated movements, and dynamics behavior of HSP90. The results of the MM-GBSA calculations suggest that the selection of GB models and empirical parameters has important influences on the predicted results and verify that van der Waals interactions are the main forces that determine inhibitor–HSP90 binding. The contributions of separate residues to the inhibitor–HSP90 binding process indicate that hydrogen-bonding interactions (HBIs) and hydrophobic interactions play important roles in HSP90–inhibitor identifications. Moreover, residues L34, N37, D40, A41, D79, I82, G83, M84, F124, and T171 are recognized as hot spots of inhibitor–HSP90 binding and provide significant target sites of for the design of drugs related to HSP90. This study aims to contribute to the development of efficient inhibitors that target HSP90 by providing an energy-based and theoretical foundation.

In this paper, a real-time assistive torque controller based on sliding-mode control is proposed for a Series Elastic Actuator (SEA)-driven lower limb assistive exoskeleton. To address the problem of the lack of buffering properties and the uneven torque output in traditional exoskeletons, a novel SEA is designed for the hip joint lower-limb exoskeleton. This structure features excellent cushioning properties and smooth torque output. On this basis, to enhance the torque tracking performance of the hip joint exoskeleton, in this study, a robust composite control strategy is proposed, which can maintain accuracy in the presence of unknown external disturbances and model parameter inaccuracies. The strategy consists of an adaptive phase oscillator for outputting the phase of the gait, a single-peak curve to provide a reference assistive torque, and a low-level controller to track the torque. The low-level controller employs Continuous Sliding-Mode Control (CSMC) to obtain a continuous control law and utilizes an Extended State Observer (ESO) to estimate the lumped disturbance. It ensures that the tracking error is asymptotically convergent with minimized chatter. The closed-loop stability of the system is theoretically proven by the Lyapunov method. The validity of the proposed algorithm is validated on a designed exoskeleton.