Figure 4.

Cation–π interactions with His serving as the cation. The binding energies and geometries of pairwise interactions between His⁺ and an aromatic residue (A) His⁰; (B) Phe; (C) Tyr; and (D) Trp. The pairwise geometries sampled from the high-resolution protein structures (whose counts are indicated by the white–brown color bar) are projected along two parameters: the angle θ₁ and the distance D between the center of the π system and the closest His nitrogen atom. The size of the symbol represnts the θ₂ angle parameter. These geometric parameters were selected because they distinguish between the pairwise interactions and enable comparisons between various types of cation–π interactions involving His (see Figure 5). The interactions between His⁺ and each of the aromatic residues were studied by selected pairs that cover the projected space. All pairwise interactions were categorized geometrically as cation–π, H-bonding, CH–π, or other, and their binding energy is shown by the rainbow color scale. The numbers overlaid onto the plot refer to the His⁺–Phe geometries, which are as per Figure 2B (for geometries 4–6) and as depicted in panel E, and thus provide additional structural information in terms of parameters Tθ₂ and P. (E) Four geometries (10–13) for pairwise interactions between the His cation and an aromatic residue. Geometry 10 depicts His⁰–His⁺ interactions in their lowest binding energy state, which is stabilized through H-bonds. Geometries 11 and 12 depict His⁺–Tyr H-bonds where His is positively charged or neutral correspondingly. Geometry 14 shows the most favorable cation–π configuration stabilized by CH–π interactions.