Mendel-Brno 2000

category image Volume: 17
Issue Number 6, Part 2
June 2000

DNA Base Amino Groups and their Role in Molecular Interactions

Amino groups of nucleic acid bases are often considered as purely planar groups, with sp2 hybridization of their nitrogen atoms and acting as conventional in-plane H-donors. The same approximation is adopted in current force fields. This view is, however, entirely incorrect [1] and leads to a neglect of interactions which are likely to be important in nucleic acids and their complexes with drugs and proteins [2-5]. Accurate quantum chemical studies convincingly show that amino groups of DNA bases are intrinsically pyramidal due to a partial sp3 hybridization of their nitrogen atoms [1,6]. The amino group hydrogen atoms are very flexible. This allows to form nonclassical interactions: out-of-plane H-bonds and amino-acceptor interactions [1-5]. Adenine amino group can also be activated by polarised water molecules when a metal cation binds to the N7 position of adenine [7]. Intrinsic nonplanarity of amino groups is essential to properly describe structure of mismatched base pairs. While canonical Watson-Crick base pairs are intrinsically planar, all G.A mismatches are substantially non-planar [3]. Flexibility of anti-anti and sheared G.A mismatches reported in experimental studies is inherent to the base pairs and is not caused by base stacking. Formation of non-classical amino-group interactions can be expected when the amino groups are not fully satisfied by planar H-bonds. Such interactions rarely occur in small molecule crystals with well developed network of H-bonds [4]. However, they are more likely to occur in large molecules [3,5].


1. P. Hobza, J. Sponer: Chem. Rev. 99, 1999, 3247.
2. J. Sponer, P. Hobza: J. Am. Chem. Soc. 116, 1994, 709.
3. J. Sponer, J. Florian, J. Leszczynski, P. Hobza: J. Biomol. Struct. Dyn. 13, 1996, 827.
4. B. Luisi, M. Orozco, J. Sponer, F.J. Luque, Z. Shakked: J. Mol. Biol. 279, 1998, 1123.
5. D. Vlieghe, J. Sponer, L. Van Meervelt: Biochemistry 38, 1999, 16443. 6. J. Sponer, P. Hobza: J. Phys. Chem. 98, 1994, 3161.
7. J Sponer, M. Sabat, J.V. Burda, J. Leszczynski, P. Hobza: J. Phys. Chem. B 103, 1999, 2528.

Jiri Sponer, Pavel Hobza

J. Heyrovsky Institute of Physical Chemistry,
Academy of Sciences of the Czech Republic,
Dolejskova 3, 182 23 Prague, Czech Republic