QM/MM investigations have been used in multiple studies related to polymerases to study the polymerization reaction of DNA . The two steps for the polymerization are the deprotonation of the O3' followed by the nucleophilic attack/phosphoryl transfer, with the latter generally reported to be the rate-limiting step. In this study, we will focus on the second part of the reaction, that is, we will concentrate on the nucleophilic attack step after deprotonation of the O3'.