eng International Academy of Ecology and Environmental Sciences Network Biology 2220-8879 2022-3-1 12 1 11 25 2 article Zoya Shafat 1 2 Anwar Ahmed 1 2 Mohammad K. Parvez 1 2 Shama Parveen 1 2 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Hepatitis E virus (HEV) of the family Hepeviridae, is a major causative agent of acute hepatitis in developing countries. The Norway rat HEV genome is organized into six open reading frames (ORFs), i.e., ORF1, ORF2, ORF3, ORF4, ORF5 and ORF6. The additional reading frame encoded protein ORF6 is attributed to life cycle of rat HEV. As ORF6 protein's remains to be explored in terms of its structural and functional implications, the following study was conceptualized to explore the prospective role of this additional genomic component of rat HEV. The detailed computational investigation was carried out for the ORF6 protein to elucidate its physiochemical properties, primary structure, secondary structure, tertiary structure and post-translational modifications, motif prediction and other functional characteristics. The in silico analysis revealed ORF6 protein as unstable, highly thermostable, hydrophobic and basic in nature. The amino acid compositional analysis revealed higher abundance of Leu, Arg, Ile and Pro amino acids in the polypeptide chain of ORF6 protein. The secondary structural analysis revealed all the three major elements, i.e., alpha-helices, beta-strands and coils. The generated 3D structural model of the ORF6 protein through homology modeling algorithm revealed mixed alpha/beta structural fold of the ORF6 protein with abundance of coils. Additionally, the structural models revealed the presence of clefts and a tunnel. The identified binding functions and the presence of several clefts suggested the commitment of ORF6 protein towards interaction with other ligand molecules. This theoretical study will facilitate towards deciphering the role of unexplored ORF6 encoded protein, thereby providing better understanding towards the pathogenesis of Norway rat HEVs. http://www.iaees.org/publications/journals/nb/articles/2022-12(1)/characteristics-of-ORF6-encoded-protein.pdf rat HEV open reading frame 6 (ORF6) physicochemical parameters structural analysis homology modeling motif prediction molecular function biological function