Microscopic modes and free energies for topoisomerase I-DNA covalent complex binding with non-camptothecin inhibitors by molecular docking and dynamics simulations

摘要: Topoisomerase I (Topo1) has been identified as an attractive target for anticancer drug development due to its central role in facilitating the nuclear process of DNA. It is essential rational design novel Topo1 inhibitors reliably predict binding structures interacting with Topo1-DNA complex. The detailed and free energies complex typical non-camptothecin have examined by performing molecular docking, dynamic simulations, energy calculations. computational results provide valuable insights into modes key factors affecting affinity. demonstrated that π–π stacking interaction DNA base pairs hydrogen bonding pivotal contributions energies, although van der Waals electrostatic interactions also significantly contribute stabilization structures. calculated are good agreement available experiment activity data. crucial obtained from present studies may future novel, more potent inhibitors.