Study of the mechanism of protonated histidine-induced conformational changes in the Zika virus dimeric envelope protein using accelerated molecular dynamic simulations.

The Zika virus has drawn worldwide attention because of the epidemic diseases it causes. It is a flavivirus that has an icosahedral protein shell constituted by an envelope glycoprotein (E-protein) and membrane protein (M-protein) in the mature virion. The multistep process of membrane fusion to infect the host cell is pH-induced. To understand the mechanism of the conformational changes in the (E-M) protein homodimer embedded in the membrane, two 200-ns accelerated dynamic simulations were performed under different pH conditions. The low pH condition weakens the interactions and correlations in both E-protein monomers and in the E-M heterodimer. The highly conserved residues, His249, His288, His323 and His446, are protonated under low pH conditions and play key roles in driving the fusion process. The analysis and discussion in this study may provide some insight into the molecular mechanism of Zika virus infection.