Computational electrophysiology simulation study of the Dengue virus viroporins.

Dengue virus, an arbovirus belongs to the Flavivirus genus is the causative agent of Dengue fever, Dengue Hemorrhagic fever and Dengue Shock Syndrome, and accounts for thousands of lives every year. Here, we have characterized three such Dengue virus proteins (NS2A, NS2B and M) which have been previously shown to possess porin like functions. An exhaustive review of the literature and multiple in silico techniques were used to identify the protein segments that are capable of generating pores. Using independent sets of Molecular Dynamics (MD) simulations and post-simulation assessments, followed by hydration analysis of the channel interiors, the potential oligomeric status of the pore-forming segments was determined. The most likely ion conducting conformation and oligomeric status were chosen after the ion conductivity mechanism of the various oligomeric topologies was examined using computational electrophysiology MD simulations. The structure of the ion channel topologies as well as their electrical characteristics, such as conductance and current through the channel, were thoroughly described. The structure-function link of the porin activity of the three Dengue virus proteins is explained in depth by this work. The data gathered from this investigation could assist target these proteins for therapeutic intervention and support future research on the ion channel function of the Dengue virus proteins.