Bioinformatics Centre, University of Pune, Ganeshkhind, PUNE 411 007. India
Development of efficacious vaccine against viruses is one of the most challenging task. Japanese encephalitis (JE) virus belongs to flaviviridae family and is a RNA virus which has a single chain envelop protein which is glycosylated at a single residue. This envelop glycoprotein (EgP) is highly antigenic and is known to have not only B-cell epitopes but also Th cell epitopes. Thus, neutralizing epitopes from this protein can be used to develop efficacious peptide vaccine. To chose proper epitopes the knowledge of 3-D structure of this 500 amino acid long EgP is essential. The sheer size of the protein as well as non availability of 3-D structure information on closely related proteins makes the task of predicting 3-D structure of EgP of JE difficult and challenging.
Recently 3-D structure of Tick Born encephalitis (TBE) EgP (partial) has been solved by single crystal x-ray diffraction which has about 47% sequence homology with JE. Using TBE as a template, the 3-D structure of JE (residues 1-450) has been built using ab- initio approach and minimal constrains on the conformation. Biosym 95.0 has been used in this model building studies. Predicted structure is analysed by using the criteria developed in- house which is based on Cą distances as well as accessibility of the residues. These results are discussed along with our approach of structure building and refinement. Essential correctness of the structure is being checked by carrying out 2D NMR studies of peptides from EgP.