Molecular dynamics of white spot syndrome virus envelope protein VP28 suggests a unique mechanism of membrane fusion.

Abstract

White spot syndrome virus (WSSV) causes white spot disease in shrimp resulting in huge economic losses. WSSV is a large enveloped virus and a trimeric envelope protein VP28 mediates its entry into host cells. The crystal structure of VP28 is reported, but the conformational transitions leading to membrane fusion are unknown. Here, atomistic molecular dynamic (MD) simulation of VP28 without its transmembrane domain was performed in water at physiological pH. The trimer opened up and dissociated multiple times without major conformational changes in its β-barrel domain, and only the N-terminal α-helical region showed sideways movement. Each monomer had equal probability of separating with accompanied increase in solvent accessible surface area and loss of H-bonds. Free energy of dissociation values revealed that VP28 trimer is three times less stable than the structurally similar Class III baculovirus envelope glycoprotein gp64, and possibly adopts a unique fusion mechanism