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

The refined models of CTL and HTL MEVs were further analyzed for their interaction with the ECD of human TLR-3 by molecular docking using the PatchDock tool. Docking conformation chosen for the CTL and HTL MEVs showed scores of 18,096 and 23,690, respectively, which were highest among all docked complexes. The highest score indicates the best geometric shape complementarity fitting of ligand and receptor predicted by the tool. The docking complex shows a fitting confirmation of both the MEVs within the ECD of TLR-3 ( Figure 8A and E). Further, the MD simulation analysis of the docked CTL-TLR-3 and HTL-TLR-3 complexes showed a very convincing reasonably stable RMSD value between ~0.4 and 0.5 nm for a given time window of 6 ns at the reasonably invariable temperature (~300 K) and pressure (~1 bar). These results indicate a stable complex formation for both MEVs with TLR-3 ( Figure 8B and F). The reasonably invariant Rg of MEV-TLR-3 complexes ( Figure 8C and G) and RMSF for all the atoms in the complexes ( Figure 8D and H) indicate that both the MEV-TLR-3 complexes are reasonably stable and are properly folded. The B-factor of CTL and HTL MEV complexes with the TLR-3 receptor is shown by rainbow color presentation in Figure 8A and