Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach

Srivastava, Sukrit; Kamthania, Mohit; Singh, Soni; Saxena, Ajay K; Sharma, Nishi

Overlapping CTL and HTL epitopes clustering with all three (CTL, HTL, and B-cell) types of epitopes or with complete epitope sequence overlap or with the highest number of HLA allele binders were identified and selected for their molecular interaction analysis with HLA alleles and TAP ( Figure 3 ). These include CTL epitopes: 47 Molecular interaction analysis of the selected epitopes with hla allele Molecular docking and MD simulation study of the selected epitopes with hla alleles Molecular docking study of all the selected epitopes with their respective HLA allele binders revealed a significantly favorable molecular interaction. Docking complexes thus formed have significantly negative binding energy, and several amino acid residues of epitopes and HLA alleles were involved in hydrogen bond formation ( Figure 4 ). To analyze the stability of binding, docking complexes were further subjected to MD simulation study with an analysis time window of 0.1 ns at the reasonably invariable temperature (~300 K) and pressure (~1 bar). The results of MD simulation for all the epitope-HLA allele complexes showed a very convincing reasonably invariant root mean square deviation (RMSD) value between ~0.1 and 0.2 nm, thus indicating stable complex formation ( Figure 5) . Moreover, the reasonably invariant radius of gyration (Rg) of the complexes ( Figure S2 ) and RMS fluctuation (RMSF) for all the atoms in the complexes ( Figure S3 ) indicate that the epitope-HLA complexes remain very stable in their folded form. B-factor of the epitope and HLA allele complexes is shown in the rainbow color presentation in Figure S4 . Most of the regions of the complexes are stable (blue) with a very small region being acceptably fluctuating (yellow and orange).