Introduction: Dengue virus is among the most widespread mosquito-borne human pathogens
with 5 different serotypes. A ratio of 3 to 7 structural and non-structural proteins is retained by the 10.7
kb viral RNA genome. The Dengue virus NS5, a non-structural and most conserved protein in the
genome plays vital role in virus replication machinery. The C-terminal RNA-dependent RNA
polymerase (RdRp) domain of NS5 has been solved experimentally in the canonical right handed
conformation that comprises of 3 sub-domains namely finger, palm and thumb. The presence of
different structural characteristics portray that RdRp adopts various conformation strategies to fulfill
Methodology: To understand the molecular switches and signaling pattern that govern conformational
functional features of NS5 RdRp domain, long-range dynamic by normal mode analysis coupled with
comparative structure analysis and Insilico docking approaches were performed.
Results: Our findings state that palm and finger are role playing and flexible sub-domains whereas the
C-terminus region of motif B influence signal transmittance and substrate binding. Different motifs of
RdRp are trivial in direct conformational transition except two C-terminal residues of motif B (L608
and T611) which modulate path signals. Signalling path indicates that dynamic clusters regulate RdRp
allosteric pathway where α10 and α20β6 loop of the finger and thumb sub-domains act as terminals in
both directions. Besides, the catalytic site, α16 connects and relay conformational signals to α12
through β5α19 loop.
Conclusion: The occurrence of motif B in four dynamic clusters 1, 2, 6 and 7 strengthen our notion
further corroborated that all motifs are trivial in direct conformational transition and motif B retains
modulation of major conformation signals.