Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/078113 doi: bioRxiv preprint Catalysis, inhibition and dynamics of Zika NS2B-NS3pro 13 the averaged RMSD values of 2.12 ± 0.16 Å, slightly higher than that of Zika (1.96 ± 0.22 Å), the Dengue NS2B has the averaged RMSD values of 8.01 ± 0.82 Å, much higher than that of Zika (6.82 ± 0.78 Å). Furthermore, although the overall patterns of the root-mean-square fluctuations (RMSF) are similar for NS3pro ( Fig 6C) and NS2B (Fig 6D) of Zika and Dengue complexes, the RMSF values averaged over four simulations of the Dengue ones are all larger than those of the Zika. In particular, the Dengue NS2B has relatively larger RMSF than Zika one over the C-terminal 7 residues (Fig 6D) . It is very interesting to observe here that although the majority of contacts of the small molecule inhibitors are with NS3pro, their removal triggers much more significant changes of dynamics of NS2B than those of NS3pro for both Zika and Dengue complexes. Again, as the current simulations only reached 100 ns, the short β-sheet still persists and remains packed with NS3pro for both Dengue (Fig. 6E) and Zika (Fig. 6F) complexes.