Structural analysis of specific fragments in the active site was carried out to determine the prevalence of catalytically competent structures sampled by both systems. K-means clustering across all three replicates of both systems with a focus on population distribution relative to catalytic distances (O3'-P) and angles (O3'-P-O3) was carried out to investigate catalytic propensity. It is seen that a considerable portion of the simulations show catalytic competency as defined by catalytic distance/angle of O3'-P<3.2Å and O3'-P-O3 >160°. Interestingly, a higher percentage of catalytically competent structures is observed for the Mg 2+ systems compared with the Mn 2+ ( Figure ). Additionally, it is seen that the system with Mn 2+ ions samples a wider distribution of both catalytic distance and angle during the simulation. Energy decomposition analysis (EDA) can reveal residues that have favorable and unfavorable interactions with the active site of both the systems. A difference of the sum of the total nonbonded intermolecular interactions (EMn-Mg=𝐸 𝑀𝑛(𝐼𝐼) 𝑛𝑜𝑛-𝑏𝑜𝑛𝑑𝑒𝑑 -𝐸 𝑀𝑔(𝐼𝐼) 𝑛𝑜𝑛-𝑏𝑜𝑛𝑑𝑒𝑑 = 53.7 𝑘𝑐𝑎𝑙 𝑚𝑜𝑙 -1 ) with respect to the incoming nucleotide, the terminal primer and the two metal co-factors, shows increased favorable interactions of the protein's environment on the system with Mg 2+ when compared to Mn 2+ . Residues having a significant contribution ( E = |5 kcal/mol|) on each system are highlighted in figure .