Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of New Drugs Against Human Topoisomerase I Receptor

Human Topoisomerase I (hTop1p) is a  ubiquitous enzyme that relaxes supercoiled DNA through a conserved  mechanism involving transient breakage, rotation, and binding. Htop1p is  the molecular target of the chemotherapeutic drug camptothecin (CPT).  It causes the hTop1p-DNA complex to slow down the binding process and  clash with the replicative machinery during the S phase of the cell  cycle, forcing cells to activate the apoptotic response. This gives  hTop1p a central role in cancer therapy. Recently, two artesunic acid  derivatives (compounds c6 and c7)have been proposed as promising  inhibitors of hTop1p with possible antitumor activity. Classical  molecular dynamics simulation was performed to assess the ability of the  two compounds to maintain a stable binding pose over time. 

The three folders contains files concerning the input and output data from the docking process of the compuonds candidates.

docking_structures_pdqt: obtained using autodock tools 4.2.6.

best_poses_output_docking: obtained using autodock vina 1.2.0.

docking_configuration_file: configuration files that define the receptor, ligand input, the center and size of the search space.

Authors: [Francesco Madeddu, Jessica Di Martino, Michele Pieroni,  Davide Del Buono, Paolo Bottoni, Lorenzo Botta, Tiziana Castrignanò, and  Raffaele Saladino]