Pol  is a heterodimer with a catalytic subunit (pol A) and a homodimeric regulatory subunit (pol B). It shares structural elements with other replicative DNA polymerases, such as the thumb, finger and palm domains (Figure ). The active site, where the addition of new incoming nucleotide occurs, consists of the terminal primer, conserved carboxylates (Asp 890 and Asp 1135 ), the incoming nucleotide, as well as two cofactors, which are generally divalent metal ions. These divalent metal ions (generally Mg 2+ or Mn 2+ ) are essential for primer extension as well as for exonuclease activity . In this study, we aim to investigate the effects of the two ions on the dynamics and kinetics of the system using computational simulations based on classical molecular dynamics (MD) , and hybrid QM/MM calculations . The sections below outline the approach we used for MD and QM/MM, elaborating on the various analyses used. Further sections discuss the results for each system, with relative perspective between the two metals and their contribution. Finally, we end with some remarks that summarize our findings.