Assessment of the Performance of the M05−2X and M06−2X Exchange-Correlation Functionals for Noncovalent Interactions in Biomolecules

TLDR

M05‑2X and M06‑2X, highly parametrized exchange‑correlation functionals, outperform common density functionals for noncovalent interactions but have not been fully benchmarked for biomolecular interactions, and their neglect of long‑range electron correlation may limit accuracy. The study tests M05‑2X and M06‑2X on nucleic acid base pairs in the JSCH‑2005 database. The authors benchmark the functionals against CCSD(T) binding energies, comparing them to PBE and PBE‑D. PBE‑D yields more accurate interaction energies overall for the JSCH‑2005 database, but M06‑2X performs better than PBE‑D for stacked base‑pair interactions.

Abstract

The highly parametrized, empirical exchange-correlation functionals, M05−2X and M06−2X, developed by Zhao and Truhlar have been shown to describe noncovalent interactions better than density functionals which are currently in common use. However, these methods have yet to be fully benchmarked for the types of interactions important in biomolecules. M05−2X and M06−2X are claimed to capture "medium-range" electron correlation; however, the "long-range" electron correlation neglected by these functionals can also be important in the binding of noncovalent complexes. Here we test M05−2X and M06−2X for the nucleic acid base pairs in the JSCH-2005 database. Using the CCSD(T) binding energies as a benchmark, the performance of these functionals is compared to that of a nonempirical density functional, PBE, and also to that of PBE plus Grimme's empirical dispersion correction, PBE-D. Due to the importance of "long-range" electron correlation in hydrogen-bonded and interstrand base pairs, PBE-D provides more accurate interaction energies on average for the JSCH-2005 database when compared to M05−2X or M06−2X. M06−2X does, however, perform somewhat better than PBE-D for interactions between stacked base pairs.