Molecular modeling and epitopes mapping of human adenovirus type 3 hexon protein.

The hexon protein of human adenovirus (HAdV) processes type-specific B-cell neutralizing epitopes. We developed a new effective, reliable approach to map these epitopes on hexon protein of HAdVs. A three-dimensional (3D) model of the HAdV3 hexon was obtained by homology modeling and refined by molecular mechanics and molecular dynamics simulations. A modified evolutionary trace (ET) analysis called reverse ET (RET) was used to predict the type-specific B-cell neutralizing epitopes. An epitope-screening algorithm based on analyzing the solvent accessibility surface (SAS) area from the 3D model and calculation of sites homology using RET was designed and implemented in the BioPerl script language. Five epitope polypeptide segments were predicted and mapped onto the 3D model. Finally five polypeptides were synthesized and the predicted epitopes were identified by enzyme-linked immunosorbent assay (ELISA) and Neutralization Test (NT). It was found that the type-specific neutralizing epitopes of HAdV3 are located at the top surface of hexon tower regions (residue numbers: 135-146, 169-178, 237-251, 262-272, 420-434). This work is of great significance to the molecular design of a multivalent HAdVs vaccine.