Structural and Functional Analysis of Dengue Virus Non-Structural Protein 5 (NS5) Using Molecular Dynamics

Dengue is an infection transmitted by the Aedes mosquito and considered a major public health concern in many tropical Asian countries, including Philippines. It caused dengue virus (DENV) which belongs to Flaviviridae family has four serotypes. The non-structural protein 5 (NS5), consists of MTase domain RdRp domain, largest most conserved among flaviviruses thus potential target against DENV. However, there are very limited studies on functional homodimer structure NS5. Through molecular dynamics, it was found that residues 458–470, 583–586, 630–637, 743–744, 890–900 monomer A 14–24, 311–315, 462–464 B undergo essential motions for conformational changes template tunnel GTP binding domain. analysis these motions, also proposed dimeric NS5 only one pair domains contribute function protein. Other residues, specifically A-ASP533, A-LYS689, A-ARG620, A-ARG688, A-SER710, B-ARG620, B-LYS689, A-GLU40, A-ARG262, A-GLU267, A-ARG673, B-ARG673, were identified play important roles information flow necessary In particular, shortest paths led identification ARG673 as residue communication between catalytic sites. Mutation this flexibility finger subdomain, may influence function. These findings serve basis future mechanism inhibition dimer drug discovery.