Density functional study of guanine and uracil quartets and of guanine quartet/metal ion complexes

The structures and interaction energies of guanine and uracil quartets have been determined by B3LYP hybrid density‐functional calculations. The total interaction energy ΔE^T of the C_4h‐symmetric guanine quartet consisting of Hoogsteen‐type base pairs with two hydrogen bonds between two neighbor bases is ?66.07 kcal/mol at the highest level. The uracil quartet with C6? H6?O4 interactions between the individual bases has only a small interaction energy of ?20.92 kcal mol^?1, and the interaction energy of ?24.63 kcal/mol for the alternative structure with N3? H3?O4 hydrogen bonds is only slightly more negative. Cooperative effects contribute between 10 and 25% to all interaction energies. Complexes of metal ions with G‐quartets can be classified into different structure types. The one with Ca²⁺ in the central cavity adopts a C_4h‐symmetric structure with coplanar bases, whereas the energies of the planar and nonplanar Na⁺ complexes are almost identical. The small ions Li⁺, Be²⁺, Cu⁺, and Zn²⁺ prefer a nonplanar S₄‐symmetric structure. The lack of coplanarity prevents probably a stacking of these base quartets. The central cavity is too small for K⁺ ions and, therefore, this ion favors in contrast to all other investigated ions a C₄‐symmetric complex, which is 4.73 kcal/mol more stable than the C_4h‐symmetric one. The distance 1.665 Å between K⁺ and the root‐mean‐square plane of the guanine bases is approximately half of the distance between two stacked G‐quartets. The total interaction energy of alkaline earth ion complexes exceeds those with alkali ions. Within both groups of ions the interaction energy decreases with an increasing row position in the periodic table. The B3LYP and BLYP methods lead to similar structures and energies. Both methods are suitable for hydrogen‐bonded biological systems. Compared with the before‐mentioned methods, the HCTH functional leads to longer hydrogen bonds and different relative energies for two U‐quartets. Finally, we calculated also structures and relative energies with the MMFF94 forcefield. Contrary to all DFT methods, MMFF94 predicts bifurcated C? H?O contacts in the uracil quartet. In the G‐quartet, the MMFF94 hydrogen bond distances N2? H22?N7 are shorter than the DFT distances, whereas the N1? H1?O6 distances are longer. © 2000 John Wiley & Sons, Inc. J Comput Chem 22: 109–124, 2001