Maria Brandl

More hydrogen bonds for the (structural) biologist

Why does a given protein structure form and why is this structure stable? These fundamental biochemical questions remain fascinating and challenging problems because the physical bases of the forces that govern protein structure, stability and folding are still not well understood. Now, a general concept of hydrogen bonding in proteins is emerging. This concept involves not only N-H and O-H donor groups, but also C-H, and not only N and O as acceptor groups, but also pi-systems. We postulate that the incorporation of the entirety of these interactions leads to a more complete description of the problem, and that this could provide new perspectives and possibly new answers.

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 ΔET of the C4h‐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 C4h‐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 C4h‐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.

Quantum-chemical analysis of C-H...O and C-H...N interactions in RNA base pairs--H-bond versus anti-H-bond pattern.

Abstract Geometries and interaction energies of unusual UU and AA base pairs with one standard hydrogen bond (H-bond) and additional C-H…O or C-H…N contacts have been determined by quantum-chemical methods taking into account electron correlation. Whereas the C-H bond length in the UU C-H…O contact increases upon complex formation (H-bond pattern), the C-H bond of the AA C-H….N interaction is shortened (anti-H-bond pattern). The same properties are found for model complexes between U or A and formaldehyde that have intermolecular C-H…acceptor contacts but no standard H-bonds. Both the C-H…acceptor H-bond and anti-H-bond interactions are attractive. A possible influence of the donor CH group charge distribution on the interaction pattern is discussed.