In silico vaccine design against type 1 diabetes based on molecular modeling of coxsackievirus B4 epitopes

Abstract

An in silico study was conducted to identify antigens with potential possibility of being a vaccine against type 1 diabetes mellitus (T1DM). A molecular mimicry between protein 2C of coxsackievirus B4 and autoantigen glutamic acid decarboxylase 65 is a significant factor in the pathogenesis of T1DM. The aim of this study was to predict the protein 2C of coxsackievirus B4 epitopes and design a vaccine against T1DM. Several web servers were used to predict continuous B cell epitopes and 8 peptides (P1–P8) were selected. Then the 3D structure of P2C was built by structural modeling using Robetta and the structure was subjected to 10 ns molecular dynamics simulation by Amber to obtain an average structure in an explicit water system. Molecular mimicry theory was confirmed by local structural alignment of modeled structure protein 2C with glutamic acid decarboxylase 65 using Swiss pdb viewer. Then conformational B cell epitope web servers were used to identify discontinuous B cells epitopes. PDBsum was used for the analysis of the protein 2C secondary structure. Finally, T cells epitopes have been predicted by the immune epitope database analysis resource (IEDB). In silico analysis of the sequence and structure retrieved by mentioned methods and web servers, revealed that two out of 8 peptides (P2 and P7 epitopes) are the best choices for the vaccine design. These results suggest that epitopes and structural features of the protein 2C of coxsackievirus B4 can be predicted and this information could be used to make novel vaccines for control of T1DM.