96 Study of the stacking of DNA homoassociates by the extended cluster approach

Abstract

Metropolis Monte Carlo method based on the extended cluster approach (Danilov, Dailidonis, van Mourik, & Fruchtl, 2011a, 2011b; Dailidonis, Danilov, Früchtl, & van Mourik, 2011) is used to investigate adenine–adenine (AA), guanine–guanine (GG), thymine–thymine (TT), and cytosine–cytosine (CC) homoassociates in a cluster consisting of 400 water molecules. The starting structures taken were AA N(7) amino symmetric, TT N(3) – O(4) symmetric, GG N(1) – O(6) symmetric, and CC N(3) amino symmetric base pairs. A water spherical cluster with the density of water at room temperature and a radius sphere equal 13.9 Å was used, which corresponds to the most difficult conditions for the formation of stacks (see Abraham, 1982). In spite of such initial conditions, it is shown that during the simulation, each base pair is transformed into a more favorable stacked configuration. The results obtained allow to observe the whole process of convergence for the first time (for more information, visit the Website http://biophys.in.ua/).

Table: Energetic characteristics of the transition from the hydrogen-bonded base pairs to the stacked associates and base stacking reaction in water cluster (in kcal/mol).

Table

Transformation	ΔU tot	ΔU ww	ΔU wb	ΔU bb
AA base pair > A/A stacked associate	−19.2	−4.7	−18.0	3.5
TT base pair > T/T stacked associate	−12.1	−6.9	−11.1	5.9
GG base pair > G/G stacked associate	−24.5	9.3	−45.2	11.4
CC base pair > C/C stacked associate	−15.8	9.9	−45.4	19.7
(CC base pair > C/C stacked associate)	−17.4	−6.4	−19.5	8.5
A + A > A/A stacked associate	−21.6	−7.5	−8.9	−5.2
T + T > T/T stacked associate	−23.6	−17.9	−1.1	−4.6
G + G > G/G stacked associate	−16.7	−0.3	−8.9	−7.4
C + C > C/C stacked associate	−38.2	−30.0	−11.2	3.0
(C + C > C/C stacked associate)	−13.7	−10.9	5.3	−8.1

It follows from this Table that all stacked associates in the water cluster are energetically more preferable to the corresponding base pairs. The changes in the interaction energies show that the water–base interaction (ΔU _wb) is the determining factor in favoring the stacked species over the base pair in an aqueous cluster. This may be due to the smaller hydrophobic surface of the stacks. The data allows us to calculate the formation energy (ΔU _tot) and its various contributions for the base stacking reaction of stacked associates investigated in the water cluster. These results are given in the Table. As can be seen, the formation of all stacked dimers was found to be favorable, with the formation energies ranging from −16.7 to −38.4 kcal/mol. The preference for the formation of these stacks results from the favorable change in the water–water interaction (ΔU _ww) and partly from the water–base (ΔU _wb) and base–base interactions (ΔU _bb) during the base association reaction. In contrast to the Watson–Crick base pairs, the formation of all stacked associates is highly favorable. The water energy change associated with the structural rearrangement of the water molecules around the bases during their association, contributes most to the stabilization of the stacks. The stacked associates are significantly less stabilized by the base–base interaction in comparison with the H-bonded base pairs. It is especially necessary to underline that the base–base interaction energy in C/C stacked associate is positive, i.e. repulsion forces operate between bases, that is conditioned by the competition between the water–water, water–base and base–base interactions. As a result the study of hydration of the base associates in any complexes with the dense packing or at the account of very small number of water molecules, as it is often done in a number of works, can result in quite erroneous results. At the same time, the use of the spherical clusters with the radius of equal 24.3 and having a volume in five times greater than the volume of 400 water molecules (see Abraham, 1982) brings base–base interaction energy to negative values (Table, values in brackets). Thus, the water–water interaction is one of the main factors promoting stacked dimer formation, and the obtained data are a direct confirmation of the crucial role of the water–water interaction in base stacking reported earlier in references.