Session: COMP Poster Session:

Reveling the mechanism of the viral capsid of mature dengue is essential to understand the vital roles in the life cycle of the virus. Capsid protein assembly in dengue may lead to the discovery of anti-viral drugs that target the vulnerable parts of the capsid. A single binding unit in the capsomer consists of two copies of E proteins and M proteins that are arranged into heterotetramers. The heterotetramers are assembled into an ordered capsid. There are many investigations of the interactions of E and M proteins. However, there are few studies on the interactions among heterotetramers and their effects in capsid assembly. Using computational approaches, this study focuses on the assembly mechanisms of the heterotetramers and the effects of pH in binding affinity of E protein in the capsid. The structure analyses lead to the identification of four binding modes of two heterotetramers that repeat periodically throughout the virus capsid. Furthermore, the electrostatic analyses show that among these four binding modes, three of them have attractive interaction and one has a repulsive interaction, making this last binding mode a potential target for future drug design. For a detailed study in the electrostatic features of viral capsid, MD simulations were performed followed by salt-bridge identification and binding energy calculations. Using the same way, pH optimum analyses were performed for a single binding unit and binding mode of E protein. It was found that the folding and binding energies of E proteins are minimum and independent of pH within the pH range between 4 to 10. This study shows a novel application of computational approaches and a promising direction to study the dengue virus capsid assembly.

Lin Li

The University of Texas at El Paso

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