Assessment of Density Functional Theory Methods for the Structural Prediction of Transition and Post-Transition...

Understanding the structure of metal-nucleic acid systems is important for many applications such as the design of new pharmaceuticals, metal detection platforms, and nanomaterials. Herein, we explore the ability of 20 density functional theory (DFT) functionals to reproduce the crystal structure geometry of transition and post-transition metal-nucleic acid complexes identified in the Protein Data Bank and Cambridge Structural Database. The environmental extremes of the gas phase and implicit water were considered, and analysis focused on the global and inner coordination geometry, including the coordination distances. Although gas-phase calculations were unable to describe the structure of 12 out of the 53 complexes in our test set regardless of the DFT functional considered, accounting for the broader environment through implicit solvation or constraining the model truncation points to crystallographic coordinates generally afforded agreement with the experimental structure, suggesting that functional performance for these systems is likely due to the models rather than the methods. For the remaining 41 complexes, our results show that the reliability of functionals depends on the metal identity, with the magnitude of error varying across the periodic table. Furthermore, minimal changes in the geometries of these metal-nucleic acid complexes occur upon use of the Stuttgart-Dresden effective core potential and/or inclusion of an implicit water environment. The overall top three performing functionals are ωB97X-V, ωB97X-D3(BJ), and MN15, which reliably describe the structure of a broad range of metal-nucleic acid systems. Other suitable functionals include MN15-L, which is a cheaper alternative to MN15, and PBEh-3c, which is commonly used in QM/MM calculations of biomolecules. In fact, these five methods were the only functionals tested to reproduce the coordination sphere of Cu²⁺-containing complexes. For metal-nucleic acid systems that do not contain Cu²⁺, ωB97X and ωB97X-D are also suitable choices. These top-performing methods can be utilized in future investigations of diverse metal-nucleic acid complexes of relevance to biology and material science.