Classical all-atom molecular dynamics (MD) simulations have been performed using the Amber18 package while the set-up as been performed with the Ambertools suite. Classical MD is used to provide a representative starting structure for the DNA duplex prior to perform the QM/MM-MD. The sequence of the chosen 16-bp duplex is represented in Figure . The ↵99bsc1 force field was employed for the nucleic acid 34 , since it notably includes the so-called Barcelona's correction for the DNA backbone . The system was solvated in a box of 7858 TIP3P water ? molecules. Potassium (K + ) counterions were added to neutralize the total charge of the box. Long-range electrostatic interactions were computed using Particle Mesh Ewald (PME) algorithm ? ? . After 1 ns of equilibration, a production run of 100 ns was performed to generate a representative starting structure, which has been chosen based on a cluster analysis of the MD trajectory.