INTERACTION OF DNA BASE PAIRS WITH DIVALENT METAL CATIONS

Jiri Sponer1, J.V. Burda 2, P. Hobza 1

1 J. Heyrovsky Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Dolejskova 3, 182~23~Prague, Czech Republic
2 Department of Chemical Physics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 2, Prague, Czech Republic

Structures and energetics of complexes between various base pairs and divalent metal cations (Mg2+, Ca2+, Sr2+, Ba2+, Zn2+ , Cd2+ and Hg2+) were characterized by high level ab initio quantum-chemical techniques. The calculations were done with and without considering the first hydration shell of the cation, the metal cations primarily interacted with the N7 site of purine bases.

- Cations can stabilize the base pairs through polarization of the proximal purine base. This mechanism has been revealed for guanine - cytosine Watson-Crick, inosine-cytosine Watson-Crick and especially guanine-guanine reverse Hoogsteen base pairs. This polarization enhancement of base pairing can contribute to stabilization of certain three dimensional structures of nucleic acids, such as G.GC triplex.

- No polarization stabilization was found in the following base pairs: adenine - thymine and 2-amino-adenine - thymine Watson-Crick, and adenine - adenine reverse-Hoogsteen. Here even a destabilization of the base pairing can be expected due to metal-cation induced activation and pyramidalization of the proximal adenine amino group. Thus, the base pairing enhancement can be ruled out for AAT triplets.

- The calculations show clear qualitative differences among various cations when interacting with different groups in biopolymers, originating in the electronic structure of the interacting species. For example, the significant difference between zinc and magnesium can be rationalized. Classical force fields are not able to treat such effects.

- Ab initio calculations represent a useful complement to experimental techniques such as crystallography, and provide a unique information about the energetics of metal-cation containing systems.

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