Domain-based homology modeling and mapping of the conformational epitopes of envelope glycoprotein of west nile virus.

Knowledge-based modeling has proved significantly accurate for generating the quality models for proteins whose sequence identity with the structurally known targets is greater than or equal to 40%. On the other hand, models obtained for low sequence identities are not reliable. Hence, a reliable and alternative strategy that uses knowledge of domains in the protein can be used to improve the quality of the model generated by the homology method. Here, we report a method for developing a 3D-model for the envelope glycoprotein (Egp) of west nile virus (WNV), using knowledge of structurally conserved functional domains amongst the target sequence (Egp of WNV) and its homologous templates belonging to the same protein family, flaviviridae. This strategy is found to be highly effective in reducing the root mean square deviation (RMSD) value at the Calpha positions of the target and its experimental homologues. The 3D structure of a protein is a prerequisite for structure-based drug design as well as for identifying the conformational epitopes that are essential for the designing vaccines. The conformational epitopes are mapped from the 3D structure of Egp of WNV modeled using the concept of an antigenic domain. A total of five such epitope regions/sites have been identified. They have been found distributed in the loop regions (surface) of the whole protein model composed of dimerization, central and immunological domains. These sites are proposed as the binding sites for HLA proteins/B-cell receptors. Binding is required to activate the immune response against WNV.