Study of common base pair mismatches in DNA: a QTAIM analysis

ESTEBAN G. VEGA HISSI; LUCAS JOEL GUTIERREZ; MATÍAS F. ANDRADA; MARIO R. ESTRADA; JUAN C. GARRO MARTINEZ

Santiago de Chile

Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists (WATOC 2014); 2014

WATOC

The complex process of DNA replication is still incompletely understood and base selectivity continues attracting scientific attention. Despite the high accuracy of this biochemical process, the formation of irregular pairs of nucleotide bases that cause spontaneous point mutations in DNA occurs. We have examined the hydrogen bonds and stacking interactions between DNA bases performing a Quantum Theory of Atoms in Molecules (QTAIM) analysis of the electronic density at the bond critical points (BCP) calculated at the BP86-D/6-311++G(d,p) level of theory. The minimal model systems consisted of combinations of adenine (A), guanine (G), cytosine (C) and thymine (T) forming Watson-Crick (WC) and irregular base pairs which were arranged in the top of each other according to B-DNA configuration. Although all the bases A, T, G and C presented higher affinity for the correct Watson-Crick counterpart, both T and A presented a notably high affinity to form mismatches with G instead of the correct WC pair. This agrees well with observations that G is incorporated into a thymine template in the absence of DNA polymerase and that these mismatches have very similar pair dissociation thermodynamics as that for the WC base pair. Albeit many BCP were involved in stacking interactions, the main contribution to the base affinity was due to the hydrogen bond network in all the studied cases. These results also showed that from calculations performed at a relatively inexpensive level of theory it is possible to explain quantitatively the different affinities between DNA bases and describe separately the hydrogen bond and stacking interactions.