Potential
Energy Surfaces of Guanine - Cytosine Base Pair and Related Tautomers:
Molecular Dynamics and Ab Initio
Study
Martin Kabeláè and Pavel Hobza1
1J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the CzechRepublic and Center for Complex Molecular Systems and Biomolecules, Prague, Czech Republic. E-mail: martin.kabelac@jh-inst.cas.cz
Introduction:
The structure of DNA is
determined among other factors by interactions between nucleic acid (NA) bases:
guanine (G) , cytosine (C), adenine (A) and thymine
(T). A theoretical study of the
interaction is important for understanding of stabilizing forces in DNA and
RNA. The interaction of NA bases in a vacuum in now being studied in experimental
laboratories [1-4] and a knowledge of the potential energy surfaces is
essential for an interpretation of experimental results. This information can
be obtained by performing correlated ab
initio calculations in combination with molecular dynamics/quenching
technique (MD/Q) [5-6].
Methods:
1. Molecular
dynamics/ quenching calculations were carried out in the NVE canonical
ensemble (Constant number of particles, volume and energy) employing Cornell et al. AMBER force field
[7], which gives results comparable with ab
initio data [8]. Due to comparable stability of several cytosine and also
guanine tautomers, all possible combinations of these tautomers should be
considered. Only the most stable (stabilization energy higher than 18
kcal/mol) and populated (population
greater than 5%) structures of base pairs were taken for further ab initio calculations.
2. Ab initio calculations. The geometries, interaction and
tautomerization energies of base pairs were determined on RI-MP2 level employing TZVPP (5s3p2d1f/3s2p1d) basis set.
Results:
In all cases planar H-bonded structures are the most
stable and most populated ones. The T-shaped and stacked structures are about
several kcal/mol less stable (typically 5-10 kcal/mol) than the structure of
the global minimum and will not be probably detectable by experimental
technique.
Among all possible
combinations of tautomers the highest stability shows canonical Watson-Crick
(WC) structure (-26.9 kcal/mol) followed by the same binding pattern with N7
keto tautomer of guanine Also other binding patterns of
ketoguanine-ketocytosine tautomers are very stable. The structures of other
combinations of tautomers are usually
less stable (about 4-5 kcal/mol) than the WC pair, including
ketoguanine-enolcytosine structure observed in the experiment[2]. An exception
is an enolguanine – ketocytosine nonplanar structure with surprisingly high
stability (-25.3 kcal/mol), but due to unfavorable geometry and stability of
the enolguanine tautomer itself, this structure will not be probably
detectable.
Summary:
We have presented a
powerful technique for scanning of potential energy surfaces of nucleic acid
base pairs, which can be used for analysis of experimental results. It is
demonstrated that the use of standard procedure based on chemical feeling and
experience is not sufficient and several mainly unusual structures can be
omitted.
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Acknowledgement:
This work was supported
by grant No. LN00A032 to the Center for Complex Molecular Systems and
Biomolecules, from MSMT of the Czech
Republic.