Probing the flexibility of Zika virus envelope protein DIII epitopes using molecular dynamics simulations

Zika virus (ZIKV) envelope protein (E) domain III (DIII) mediates viral attachment and fusion. The DIII facilitates cell receptor recognition, and includes several ZIKV antibody epitopes. The DIII is also considered as an antigenic target for ZIKV-neutralising antibodies. Understanding the flexibility and dynamical behaviour of ZIKV DIII can aid the design of vaccines against ZIKV. Using molecular dynamics (MD) simulations, the flexibility of DIII and its epitopes were characterised. The final structure from a 100 ns-long MD simulation was docked to anti-DIII ZIKV Fabs (ZV67 and ZV64). Interestingly, the analysis of the MD simulations revealed that the residues of the C-C’ loop and the ABDE sheet epitopes (epitopes for moderately neutralising ZV64 and weakly neutralising ZV2 mAbs, respectively) were highly flexible, whereas the LR epitope for strongly neutralising ZV67 mAb was rigid.