Structural insights into HCV glycoprotein E1-E2 interactions: a biomolecular modelling approach

Abstract

The Hepatitis C virus is a leading contributor to various liver related diseases such as cirrhosis and liver cancer. It creates considerable challenges for treatment due to its extensive genetic variability. As a result, the virus is able to mutate rapidly and evade the immune system of the host's body, complicating the formulation of effective vaccines. The E1-E2 heterodimer complex is a potential target for therapeutic development as they contain several critical regions that are essential for the viral infection process. However, the dynamic behaviour of the glycoprotein complex is not yet completely understood. In the present study titled as the “Structural Insights into HCV Glycoprotein E1-E2 Interactions: A Biomolecular Modelling Approach”, the main objective is to better understand how the hepatitis C virus (HCV) envelope glycoproteins E1 and E2 interact with each other at the molecular level using advanced biomolecular modeling techniques. In our research, we explored the dynamic behaviour of these two glycoproteins along with their critical regions. Here, we investigated the structural dynamics of E1 and E2 through molecular simulations of two distinct systems: an apo form consisting solely of the proteins, and a complex form containing the proteins along with two N-linked glycans positioned at their interface. These specific glycans were included based on their known roles in promoting glycoprotein binding, enhancing structural stability, and supporting proper folding. Gaussian accelerated molecular dynamics (GaMD) was employed for 1 microsecond in triplicate to observe the conformational variation in both apo and complex structures. By comparing the simulation outcomes of both systems, we aim to uncover the structural and dynamic changes induced by the presence of these glycans, providing deeper insight into their role in stabilizing the E1-E2 interaction.