Molecular insights into the Y-domain of hepatitis E virus using computational analyses

Hepatitis E virus (HEV) of the family Hepeviridae is a major causative agent of acute hepatitis in developing countries. The Y-domain is derived from multi-domain non-structural polyprotein encoded by open reading frame 1 (ORF1). Previous studies have demonstrated the essentiality of Y-domain sequences in HEV life cycle; however, its function remains completely unexplored. The following study was thus conceptualized to examine the detailed computational investigation for the putative Y-domain to estimate its phylogenetic assessment, physiochemical properties, structural and functional characteristics using in silico analyses. The phylogenetic assessment of Y-domain with a vast range of hosts indicated that the protein was very well conserved throughout the course of evolution. The Y-domain was found to be unstable, hydrophilic and basic in nature with high thermostability value. Structural analysis of Y-domain revealed mixed α/β structural fold of the protein having higher percentage of alpha-helices. The three-dimensional (3D) protein model generated through homology modelling revealed the presence of clefts, tunnels and pore. Gene ontology analysis predicted Y-domain protein’s involvement in several binding and catalytic activities as well as significant biological processes. Mutations in the conserved amino acids of the Y-domain suggested that it may stabilize or de-stabilize the protein structure that might affect its structure–function relationship. This theoretical study will facilitate towards deciphering the role of unexplored Y-domain, thereby providing better understanding towards the pathogenesis of HEV infection.