Parametrization of DFTB3/3OB for Magnesium and Zinc for Chemical and Biological Applications

We report the parametrization of
the approximate density functional
theory, DFTB3, for magnesium and zinc for chemical and biological
applications. The parametrization strategy follows that established
in previous work that parametrized several key main group elements
(O, N, C, H, P, and S). This 3OB set of parameters can thus be used
to study many chemical and biochemical systems. The parameters are
benchmarked using both gas-phase and condensed-phase systems. The
gas-phase results are compared to DFT (mostly B3LYP), ab initio (MP2 and G3B3), and PM6, as well as to a previous DFTB parametrization
(MIO). The results indicate that DFTB3/3OB is particularly successful
at predicting structures, including rather complex dinuclear metalloenzyme
active sites, while being semiquantitative (with a typical mean absolute
deviation (MAD) of ∼3–5 kcal/mol) for energetics. Single-point
calculations with high-level quantum mechanics (QM) methods generally
lead to very satisfying (a typical MAD of ∼1 kcal/mol) energetic
properties. DFTB3/MM simulations for solution and two enzyme systems
also lead to encouraging structural and energetic properties in comparison
to available experimental data. The remaining limitations of DFTB3,
such as the treatment of interaction between metal ions and highly
charged/polarizable ligands, are also discussed.