Predicting Noncovalent Interactions between Aromatic Biomolecules with London-Dispersion-Corrected DFT

Within the framework of Kohn−Sham density functional theory, interaction energies of hydrogen bonded
and π−π stacked supramolecular complexes of aromatic heterocycles, nucleobase pairs, and complexes of
nucleobases with the anti-cancer agent ellipticine as well as its derivatives are evaluated. Dispersion-corrected
atom-centered potentials (DCACPs) are employed together with a generalized gradient approximation to the
exchange correlation functional. For all systems presented, the DCACP calculations are in very good agreement
with available post Hartree−Fock quantum chemical results. Estimates of 3-body contributions (<15% of
the respective interaction energy) and deformation energies (5−15% of the interaction energy) are given.
Based on our results, we predict a strongly bound interaction energy profile for the ellipticine intercalation
process with a stabilization of nearly 40 kcal/mol (deformation energy not taken into account) when fully
intercalated. The frontier orbitals of the intercalator−nucleobase complex and the corresponding non-intercalated
nucleobases are investigated and show significant changes upon intercalation. The results not only offer some
insights into the systems investigated but also suggest that DCACPs can serve as an effective way to achieve
higher accuracy in density functional theory without incurring an unaffordable computational overhead, paving
ways for more realistic studies on biomolecular complexes in the condensed phase.