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

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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.

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Acknowledgement

This research is supported by University of Isfahan (Grant No: 97886/90).

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran

    Mahsa Taherzadeh & Abolghasem Esmaeili

  2. Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

    Abolghasem Esmaeili & Mohamad Reza Ganjalikhany

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  1. Mahsa Taherzadeh
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  2. Abolghasem Esmaeili
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  3. Mohamad Reza Ganjalikhany
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Correspondence to Abolghasem Esmaeili.

Electronic supplementary material

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Figure S1. Sequence of P2C of CVB4 (TIFF 137 kb)

Figure S2: Ramachandran plot obtained for modeled structure by PROCHECK (JPEG 105 kb)

Figure S3: Root mean square deviation (Å) of P2C versus MD simulation time (ns) (JPEG 71 kb)

13721_2016_112_MOESM4_ESM.pdf

Figure S4: Accessible surface area plot for modeled P2C. Colour index: Blue: Positive charged residues (R, K, H), Red: Negative charged residues (D, E), Green: Polar uncharged residues (G, N, Y, Q, S, T, W), Yellow: Cysteine, Gray: Hydrophobic residues (All others) (PDF 33 kb)

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Taherzadeh, M., Esmaeili, A. & Ganjalikhany, M.R. In silico vaccine design against type 1 diabetes based on molecular modeling of coxsackievirus B4 epitopes. Netw Model Anal Health Inform Bioinforma 5, 5 (2016). https://doi.org/10.1007/s13721-016-0112-y

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