Evaluation of the Effects of Novel 1-Oxa-4-azaspironenone Derivatives with Antitumor Activity: Quantum Mechanics/Molecular Mechanics, Molecular Docking, and Molecular Dynamics Simulation Studies

ONIOM2 approach put together molecular dynamics simulations and molecular docking was conducted to the investigation of the interaction of some the novel azaspironenone derivatives with Caspase-3 protein. The active sites of the protein that resulted from molecular docking are applied for computations of ONIOM2 and molecular dynamics. The best pose of the configuration of studied azaspironenone derivatives in the active sites of Caspase-3 protein results in negative binding energies. Also, the stability of the compounds was confirmed by ONIOM2 calculations. The data showed that the residues of Gly94, Thr34, and Cys135 participated in the formation of hydrogen bonds. In addition, MD simulation was done on the stable complexes with high binding energy to recognize the structural changes on azaspironenone derivatives-Caspase-3 protein complexes. The silico studies illustrated that the properties of docking of azaspironenone derivatives could be used as a potential therapeutic agent against the A549 human lung cancer cells.