The QM region for both systems include D890, V891, D892, H1134, D1135, E1136, dT3', dCTP, the two metal ions and coordinating water molecules to both metals and the triphosphate part of dCTP. Five structures for each of the systems were selected as starting structures for reactant optimization based on catalytic competency. Once the QM/MM optimizations of the reactant were completed, the lowest energy representative was used in each system to generate the product structure in silico, which was subsequently optimized. Once the optimized product was obtained, QSM was utilized to obtain the minimum energy path for the reaction. Overlaying the reactant, approximate transition state and product of each of the two systems shows that they have similar conformations (Fig. )