  Non structural protein 3 (NS3) helicase from hepatitis C virus is an enzyme
that unwinds and translocates along nucleic acids with an ATP-dependent
mechanism and has a key role in the replication of the viral RNA. An
inchworm-like mechanism for translocation has been proposed based on crystal
structures and single molecule experiments. We here perform atomistic molecular
dynamics in explicit solvent on the microsecond time scale of the available
experimental structures. We also construct and simulate putative intermediates
for the translocation process, and we perform non-equilibrium targeted
simulations to estimate their relative stability. For each of the simulated
structures we carefully characterize the available conformational space, the
ligand binding pocket, and the RNA binding cleft. The analysis of the hydrogen
bond network and of the non-equilibrium trajectories indicates an ATP-dependent
stabilization of one of the protein conformers. Additionally, enthalpy
calculations suggest that entropic effects might be crucial for the
stabilization of the experimentally observed structures.

Biomolecules;Biological Physics;Chemical Physics