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 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.