Molecular modelling of HPV E6 protein reveal new potential inhibitors against high-risk Human Papillomavirus: Supporting Information

<b>Abstract:</b> High-risk strains of human papillomavirus (HPV) have been identified as the etiologic agent of some anogenital tract, head, and neck cancers. Although prophylactic HPV vaccines have been approved; it is still necessary a drug-based treatment against the infection and its oncogenic effects. The E6 oncoprotein is one of the most studied therapeutic targets of HPV, it has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6 can promote the degradation of p53, a tumor suppressor protein, through the interaction with the cellular ubiquitin ligase E6AP. Therefore, preventing the formation of the E6-E6AP complex is one of the main strategies to inhibit the viability and proliferation of infected cells. Herein, <b>we propose an <i>in silico</i> pipeline to identify small-molecule inhibitors of the E6-E6AP interaction</b>. Virtual screening was carried out by predicting the ADME properties of the molecules and performing ensemble-based docking simulations to E6 protein followed by binding free energy estimation through MM/PB(GB)SA methods. Finally, the top-three compounds were selected, and their stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction was corroborated by molecular dynamics simulation. Therefore, this pipeline and the identified molecules represent a new starting point in the development of anti-HPV drugs.<br>This<b> fileset </b>contains raw data from molecular dynamics simulations of HPV-16 E6 protein, including initial files and backbone trajectories. Also includes the initial compound library, ADME properties predictions, molecular docking results and hit compounds in mol2 format.<br><br>