INVESTIGADORES
GUTIERREZ lucas Joel
congresos y reuniones científicas
Título:
Study of common base pair mismatches in DNA: a QTAIM analysis
Autor/es:
ESTEBAN VEGA-HISSI; GUTIÉRREZ LUCAS JOEL; ANDRADA MATIAS; ESTRADA MARIO; GARRO JUAN MARTINEZ
Reunión:
Congreso; 10th Congress of theWorld Association of Theoretical and Computational Chemists (WATOC); 2014
Resumen:
Study of common base pair mismatches in DNA: a QTAIM analysis
Esteban G. Vega-Hissia, Lucas J. Gutierrez b,
Matias F. Andrada a, Mario R. Estradaa, Juan C. Garro
Martineza
aÁrea de QcaFca, F. Q. B.y F., Univ. Nac. de San Luis; e-mail: egvega@uns.edu.ar, mfandra@unsl.edu.ar, mestrada@unsl.edu.ar, jcgarro@unsl.edu.ar; bLab. Estruct. Mol y Prop., F.C.Ex. y
Nat. y A., Univ. Nac. del Nordeste; e-mail: lucasg@unsl.edu.ar
Abstract
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 [1].
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
(see Figure 1).
Although all the bases A,
T, G and C presented higher affinity for the correct Watson-Crick counterpart
(i.e. T, A, C and G, respectively), 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 [2]. Albeit many BCP were involved in stacking
interactions, the main contribution to overall 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.
References:
[1]
I. I. Cisse, H. Kim, T. Ha, Nat. Struct. Mol. Biol. 19 (2012) 623.
[2] J. Poater et al.,
ChemComm 47 (2011) 7326.