The top screened compound complexes with the helicase were minimized with CHARMm force field. The topology files of the ligands were prepared from Swissparam () and minimized in Gromacs2020 () . Docked complexes of ligands and the helicase protein were used as starting geometries for MD simulations. Simulations were carried out using the GPU accelerated version of the program with the CHARMm force field I periodic boundary conditions in the ORACLE server. Docked complexes were immersed in a truncated octahedron box of TIP3P water molecules. The solvated box was further neutralized with Na+ or Cl-counter ions using the tleap program. Particle Mesh Ewald (PME) was employed to calculate the long-range electrostatic interactions. The cut-off distance for the long-range van der Waals (VDW) energy term was 12.0 Å. The whole system was minimized without any restraint. The complexes were subjected to 2500 cycles of steepest descent minimization followed by 5000 cycles of conjugate gradient minimization. After system optimization, the MD simulations were initiated by gradually heating each system in the NVT ensemble from 0 to 300 K for 50 ps using a Langevin thermostat with a coupling coefficient of 1.0/ps and with a force constant of 2.0 kcal/mol•Å2 on the complex. Finally, a production run of 20 ns of MD simulation was performed under a constant temperature of 300 K in the NPT ensemble with periodic boundary conditions for each system. During the MD procedure, the SHAKE algorithm was used to constrain all covalent bonds involving hydrogen atoms. The time step was set to 2 fs. The structural stability of the complex was monitored by the RMSD and RMSF values of the backbone atoms of the entire protein. Calculations were also performed for up to 100 ns on a few compounds to ensure that 20ns was sufficiently long for convergence. Duplicate production runs starting with different random seeds were also run to allow estimates of binding energy uncertainties to be obtained.