Potential Natural Inhibitor Bioactivities against High-Risk HPV-16, HPV-18 and HPV-52 of E6 Oncoprotein through Molecular Docking

Abstract

Human papillomavirus (HPV) is known as the main cause of cervical cancer. Most sexually active women and men might be high risk infected by HPV. In Indonesia, HPV-16 and 18 types are equally common in the general population associated with cervical cancer. HPV-52 is the most prevalent type in the general population worldwide. Some natural products have been identified as promising sources as inhibitor agents for treatment and prevention of cancers in recent years. Indonesia is abundant of original plants with bioactive compounds that play role as anticancer, such as red fruit, turmeric, god's crown, ground cherry and white turmeric. The aim of this research is to structure-based screen the interaction between protein E6 from HPV-16, 18 and 52 strains with natural compounds through molecular docking. Out of five natural compounds that we studied, we found the highest binding energy to interact with E6 HPV-16 is daphnoretin (-6.8 kcal/mol), HPV-18 and 52 is ?-cryptoxanthin -6.5 kcal/mol and -6.6 kcal/mol. Molecular dynamics simulations provide a platform for capturing the structures, motions, and interactions of biological macromolecules in full atomic details. The accuracy of such simulations, however, is critically dependent on the force field the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. The results suggest that the third profile of protein E6 HPV-18 and 52 tend to be stable, while E6 HPV-16 was not stable, this might be due to the differences in the ligand interaction.