Assessment of Density Functional Theory Methods for the Structural Prediction of Transition and Post-Transition Metal-Nucleic Acid Complexes

Understanding the structure of metal-nucleic acidsystemsis important for many applications such as the design of new pharmaceuticals,metal detection platforms, and nanomaterials. Herein, we explore theability of 20 density functional theory (DFT) functionals to reproducethe crystal structure geometry of transition and post-transition metal-nucleicacid complexes identified in the Protein Data Bank and Cambridge StructuralDatabase. The environmental extremes of the gas phase and implicitwater were considered, and analysis focused on the global and innercoordination geometry, including the coordination distances. Althoughgas-phase calculations were unable to describe the structure of 12out of the 53 complexes in our test set regardless of the DFT functionalconsidered, accounting for the broader environment through implicitsolvation or constraining the model truncation points to crystallographiccoordinates generally afforded agreement with the experimental structure,suggesting that functional performance for these systems is likelydue to the models rather than the methods. For the remaining 41 complexes,our results show that the reliability of functionals depends on themetal identity, with the magnitude of error varying across the periodictable. Furthermore, minimal changes in the geometries of these metal-nucleicacid complexes occur upon use of the Stuttgart-Dresden effectivecore potential and/or inclusion of an implicit water environment.The overall top three performing functionals are & omega;B97X-V, & omega;B97X-D3(BJ),and MN15, which reliably describe the structure of a broad range ofmetal-nucleic acid systems. Other suitable functionals includeMN15-L, which is a cheaper alternative to MN15, and PBEh-3c, whichis commonly used in QM/MM calculations of biomolecules. In fact, thesefive methods were the only functionals tested to reproduce the coordinationsphere of Cu2+-containing complexes. For metal-nucleicacid systems that do not contain Cu2+, & omega;B97X and & omega;B97X-D are also suitable choices. These top-performing methodscan be utilized in future investigations of diverse metal-nucleicacid complexes of relevance to biology and material science.

Automated summary

Understanding the structure of metal-nucleic acid systems is important for various applications. This study investigated the ability of 20 density functional theory (DFT) functionals to reproduce the crystal structure geometry of these complexes. The results showed that the reliability of functionals depends on the metal identity, and certain functionals performed well in describing the structure of a range of metal-nucleic acid systems.