Computational Evaluation of Phytochemicals from Chamaecyparis obtusa var. formosana as Potential HSP90 Inhibitors

The identification of novel inhibitors targeting Heat Shock Protein 90 (HSP90) remains a promising strategy in anticancer drug discovery. In this study, three natural compounds from Chamaecyparis obtusa var. formosanarecently, which have recently been introduced to the literature, were subjected to a comprehensive computational investigation, including Density Functional Theory (DFT) calculations, molecular docking studies, molecular dynamics (MD) simulations and binding free energy calculations. DFT calculations were employed to optimize molecular geometries and generate molecular electrostatic potential (MEP) maps. Molecular docking studies were then performed to evaluate the interaction profiles of the compounds with HSP90. After performing molecular docking studies, molecular dynamics (MD) simulations were conducted to assess the stability of the ligand-protein complexes and to determine the binding free energies using MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. MD simulations corroborated the formation of stable ligand-receptor complexes, as all three compounds maintained structural stability throughout the simulation period. Remarkably, two of the investigated compounds exhibited a higher binding affinity than the reference molecule, BIIB021 suggesting enhanced inhibitory potential. These results highlight the potential of the studied natural compounds as promising HSP90 inhibitors and provide a solid foundation for future experimental validation and drug development efforts.