Molecular Dynamics Simulation Study on the Effect of Oxali-Palladium as a Catalytic Inhibitor of Human Topoisomerase IIα

Among the many anticancer agents targeting topoisomerase IIα enzyme, palladium (II) analogues have gained in popularity as a promising enzyme inhibitor. In this article, molecular docking method and molecular dynamics (MD) simulations were employed to study the mechanism through which oxali-palladium (oxali-Pd) inhibits the enzymatic activity of human topo IIα. The results of docking simulation confirm the inhibitory effects of oxali-Pd on the catalytic core of topoisomerase IIα enzyme through a non-competitive process. Also, it is suggested that oxali-Pd might intercalate within the DNA bases according to the topo IIα dynamicity as well. The results of MD simulations reveal that oxali-Pd is surrounded by Arg713, Ser714, Lys723, GLN726, Ser 763, Met766, Thr767, Asn770, Leu771, Glu854, Gly855, and Arg929 residues of protein. The average value of Δ G solv is about − 93.1 kJ.mol −1 for protein and − 95.1 kJ.mol −1 for complex. The average values of Coulombic and Lennard–Jones interaction energies are calculated to be about − 78.1 ± 18.9 and − 81.8 ± 10.2 kJ.mol −1 , respectively. These interaction energy values demonstrate the both electrostatic and van der Waals forces are important in complex formation between topo IIα protein and oxali-Pd molecule. Therefore, based on the data obtained from this study, oxali-Pd acts as a catalytic inhibitor of human topo IIα and is not a poison to the enzyme.