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

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

In particular, the Zika NS2B has much larger RMSF over the N-terminal 6 residues C-terminal 22 residues (Fig 4D) . A close inspection of the structure snapshots reveals that although the Dengue NS2B residues Glu80-Glu90 have large conformational fluctuations, the residues Gln93-Thr94-Leu95 constantly have close contacts with the NS3pro residues Leu31-Gly32-Tyr33-Ser34 in the whole 100-ns simulations (Fig 4E) , and consequently have small RMRF over this short fragment (Fig 4D) . By a sharp contrast, the Zika residues Pro93-Met94-Arg95 corresponding to Dengue Gln93-Thr94-Leu95 lose the contact with NS3pro after 10 ns and consequently the Zika NS2B C-region becomes highly exposed (Fig. 4F ). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/078113 doi: bioRxiv preprint structure snapshots of Zika NS2B (Fig 5B) reveal that only after 30 ns, a short β-sheet is formed with two β-strands over residues Val76-Asp79 and Gly82-L86, which is further illustrated by the structure snapshots of Zika NS2B-NS3pro complex (Fig. 5C ). This is a significant finding as in the closed conformation, this β-sheet further get packed to NS3pro, even with residues Ser80-Gly81-Asp82 directly contacting the inhibitor (25) . Unfortunately, the formation of such packing is expected to occur at least over µs-ms time scale, which still remains challenging to be simulated by MD.