Structure-Based Virtual Screening for Small-Molecule Inhibitors of HPV-16 E6

Abstract Human papillomavirus type 16 E6 (16E6) is a key oncogenic protein in HPV-associated cancers which enables tumor growth by promoting ubiquitination and degradation of host tumor suppressor p53. This study seeks to find inhibitors of 16E6 protein-protein interaction (PPI) through structure-based virtual screening of multiple small-molecule PPI ligand libraries. Through ADMET screenings, molecular dynamics simulations, and MM/GBSA energy calculations, ten druglike compounds were discovered. Through more in-depth analysis, three of those candidates were found to have demonstrated more favorable binding energies while maintaining comparable stability within the 16E6 pocket.