In silico molecular study of hepatitis B virus X protein as a therapeutic target

The Hepatitis B virus is a leading cause of liver cirrhosis and hepatocellular carcinoma. HBx viral protein is considered a contributor to pathogenesis and hepatocarcinogenesis. This study aimed to screen the effect of some antiviral compounds to target HBx protein for inhibition of its function. Here, molecular docking, molcular dynsmic simulation, MM/GBSA and T-SNE methods were applied to study the complex stability and to cluster the conformations that generated in the simulation. Among the 179 compounds screened in this study, three antiviral agents (SC75741, Punicalagin, and Ledipasvir) exhibited the lowest docking energy and best interaction. Among these compounds, SC75741 was identified as a potent inhibitor of HBx that showed the best and most stable interaction during molecular dynamic simulation, and blocking a region near to HBx helix resides (aa 88-100) that is associated with cell invasion. The analysis of relative binding free energy through MM/GBSA for molecular dynamic simulation results revealed binding energy -9.9 kcal/mol for SC75741, -11 kcal/mol for Punicalagin, and -10.1 kcal/mol for Ledipasvir. These results elucidate the possible use of these compounds in the research for targeting HBx.Communicated by Ramaswamy H. Sarma.