Our interests in the nonstructural protein 3 (NS3) enzyme of Flaviviridae viruses (e.g. Zika, Hepatitis C, and dengue viruses) are twofold. From a fundamental standpoint, the helicase domain of NS3 is a model system for theoretical modeling of energy transduction through a molecular motor. Additionally, the NS3 helicase plays a pivotal during the replication of the viral genome, making the enzyme a viable target for antiviral drug development. A range of multi-scale computational methods have been used to model the ATP hydrolysis cycle for the dengue virus NS3 helicase. We are currently expanding this study to the Zika virus helicase. Insight gained from these simulations will provide mechanistic details about the energy transduction process as well as allow us to identify important protein motifs to use as targets for drug-binding and mutational studies.