Evaluation of stabilization energies in π-π and cation-π interactions involved in biological macromolecules by ab initio calculations

Non-covalent interactions involving aromatic rings contribute significantly to the stability of three-dimensional structures of biological macromolecules. Therefore, accurate descriptions of such interactions are crucial in understanding the functional mechanisms of biological molecules. However, it is also well known that, for some cases where van der Waals interactions make a dominant contribution, conventional ab initio electronic structure calculations, such as density functional theory, do not produce accurate interaction energies. In this study, we evaluated molecular mechanics (MM) calculations for two types of interactions involving aromatic rings, π-π interactions and cation-π interactions, by comparing our results with those obtained by advanced ab initio calculations at the coupled-cluster with singles, doubles and perturbative triples level. In structures with stacked aromatic rings, interaction energies obtained by MM calculations are overestimated. On the other hand, for cation-π interactions, the energies in MM calculations are significantly underestimated. In both cases, addition of an induction energy based on polarization effects also fails to improve the estimate given by MM calculations. The results indicate that current effective pairwise potentials are inappropriate to represent π-π and cation-π interactions.