Conformational dynamics of Dengue Helicase NS3

CAROLINA SARTO; SERGIO KAUFMAN; DARIO ESTRIN; MEHRNOOSH ARRAR

Ciudad Autónoma de Buenos Aires

Congreso; Protein Biophysics at the End of the World v2; 2017

Dengue represents a substantial public health burden, particularly in low-resource countries. Non-structural protein 3 is a multifunctional protein critical in the virus life cycle that has been identified as a promising anti-viral drug target. Despite recent crystallographic studies of the DENV NS3 helicase domain (NS3hel), no structural nucleotide-dependent differences have been identified, such that the coupled ATPase and helicase activities of the NS3hel remain mechanistically unclear. Here we use molecular dynamics simulations to explore the nucleotide-dependent conformational landscape of the DENV NS3 helicase and identify substantial changes in the protein flexibility during the ATP hydrolysis cycle.