Accuracy of the fragment molecular orbital (FMO) calculations for DNA: Total energy, molecular orbital, and inter-fragment interaction energy

The fragment molecular orbital (FMO) method can calculate the electronic structure of macromolecules such as DNA by dividing them into several fragments and introducing suitable approximations. To establish guiding principles for FMO calculation of DNA, benchmark tests were performed for several small DNA models consisting of one or two bases or two base pairs. The effects of several factors on the accuracy of FMO calculations were investigated, including the methods used to fragment the nucleotide units, approximations for the electrostatic potential, charge neutralization, and electron correlation. It was found that charge neutralization is indispensable for the reliable calculation of energies and spatial distribution of molecular orbitals, but not necessarily so for inter-fragment interaction energy analyses, such as calculation of the base–base interaction. The electrostatic approximations were shown to have only an insignificant effect on the qualitative nature of the calculations. It was also confirmed that the base–base stacking energy can be reproduced semi-quantitatively by the Møller–Plesset second-order perturbation (MP2) method though with some overestimation, and that the overestimation can be alleviated by the spin-component-scaled MP2 method.