Binding Mechanism of Inhibitors to Heat Shock Protein 90 Investigated by Multiple Independent Molecular Dynamics Simulations and Prediction of Binding Free Energy.

ABSTRACT: 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 inf

SUBMITTER: Yang F 

PROVIDER: S-EPMC10304427 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature