Possible scenarios of DNA double-helix unzipping process in single-molecule manipulation experiments

Abstract

Single-molecule experiments on DNA unzipping are analyzed on the basis of the mobility of nucleic bases in complementary pairs. Two possible scenarios of DNA double-helix unzipping are proposed and studied, using the atom-atom potential function method. According to the first scenario, the base pairs transit into a 'preopened' metastable state and then fully open along the 'stretch' pathway. In this case, the DNA unzipping takes place slowly and as an equilibrium process, with the opening energies being similar to the energies obtained in thermodynamic experiments on DNA melting. The second scenario is characterized by higher opening forces. In this case, the DNA base pairs open directly along the 'stretch' pathway. It follows from our calculations that, in this scenario, the enthalpy difference between the A[Formula: see text]T and G[Formula: see text]C base pairs is much higher than in the first case. The features of the first unzipping scenario show that it can play a key role during the process of DNA genetic information transfer in vivo. It follows from our study that a peculiarity of the second scenario is that it can be used for the development of faster methods for reading genetic information in vitro.

The Possibility of Blocking the Process of DNA Base Pairs Opening by Hydrogen Peroxide

“…At the same time, the difference in the interaction energy for G·C pair is significant, which is due to the anomalous contribution of the Coulomb interaction. More details of the necessity of using the dependency (5) are discussed in [29]. It was shown in [11] that the calculation results of the water-water and peroxide-water complexes with the use of the dependence (5) are much closer to the results of quantum-chemical calculations than without this dependence.…”

“…In the work [29], it has been shown that during the unzipping of a double helix, depending on the opening velocity, base pairs can open as along the 'stretch' pathway, as well as along the 'opening' pathway. And in the work [35] it was shown that during unzipping process configurations of base pairs that are stabilized by water bridges occur.…”

On a possibility of the blocking of DNA specific recognition sites by hydrogen peroxide molecules during ion beam therapy

“…In this case, the energy of nucleic base blocking by hydrogen peroxide molecule is comparable to the energy of the complementary pairs formation. [23] To sum up, depending on the form of DNA, binding to the DNA bases in the solution can occur both from the sides of major and minor grooves. By this means there are sites of nucleic bases, where binding to hydrogen peroxide is much more advantageous than that of a water molecule.…”

“…1 and 2), in the framework of AAPFh approach the energy minima values, as well as spatial configurations of the molecules, are consistent with the corresponding works much better than the same calculations carried out in a gas phase. Also in the work [23] it was shown the necessity of use of dependence (5) when calculating interactions in nucleic base pairs to avoid anomalous Coulomb contributions. Due to these facts, all the following calculations in the framework of AAPF method we perform taking into account the dependence (5).…”