Computational screening identifies depsidones as promising Aurora A kinase inhibitors: extra precision docking and molecular dynamics studies

The Aurora kinases play crucial roles in regulating mitotic progression and have implications in various diseases, including cancer. In this study, we explored the potential of depsidone analogues as inhibitors of Aurora A kinase through computational methods. A molecular docking studies of 260 depsidone molecules against Aurora A kinase, were conducted using extra precision docking mode of Glide. Three molecules, parmosidone A, chaetosidone A, and parmosidone E, showed promising docking scores compared to the reference inhibitor. These compounds exhibited strong interactions with the binding site of Aurora A kinase, involving hydrogen bonds and hydrophobic interactions. To further evaluate the stability of these interactions, we performed molecular dynamics simulations for 100 nanoseconds. RMSD analysis indicated that all compounds maintained relatively stable interactions with the protein throughout the simulation period. Notably, parmosidone A and chaetosidone A exhibited minimal fluctuations after an initial equilibration phase. RMSF analysis revealed that certain protein residues showed high fluctuations but were not crucial for inhibitor binding. Protein-ligand interaction analysis demonstrated that water bridges and hydrogen bonds played significant roles in the interactions between the compounds and Aurora A kinase. Overall, our computational assessments suggest that depsidone analogues, particularly parmosidone A and chaetosidone A, have potential as inhibitors of Aurora A kinase. These findings provide insights into the molecular interactions of these compounds and open new avenues for targeting Aurora A kinase in cancer therapy.