The residues in the active site showed some distortion after the removal of restraints. Hence, these residues, namely the incoming nucleotide, Asp 890 , Asp 1135 , the two metal ions and the 3'-OH terminus were restrained with an additional 0.25 kcal/mol/Å 2 for an additional 25 ns. Once the system was stabilized, the restraints were removed and both the systems were subjected to 500 ns NPT MD in triplicate with a 2 fs time step, resulting in a total on 1.5 s. All bonds involving hydrogen were treated with SHAKE . Long-range coulomb interactions were handled with smooth particle mesh Ewald (PME) method and long-range van der Waals interactions are approximated using the default isotropic correction (in AMBER) with a 10 Å cutoff for non-bonded interactions.