Genesis of Open States Zones in a DNA Molecule Depends on the Localization and Value of the Torque

Abstract

The formation and dynamics of the open states in a double-stranded DNA molecule are largely determined by its mechanical parameters. The main one is the torque. However, the experimental study of DNA dynamics and the occurrence of open states is limited by the spatial resolution of available biophysical instruments. Therefore, in this work, on the basis of a mechanical mathematical model of DNA, calculations of the torque effect on the process of occurrence and dynamics of open states were carried out for the interferon alpha 17 gene. It was shown that torsion action leads to the occurrence of rotational movements of nitrogenous bases. This influence is nonlinear, and an increase in the amplitude of the torsion action does not lead to an automatic increase in the amplitude of rotational movements and an increase in the zones’ open states. Calculations with a constant torsion moment demonstrate that open states zones are more often formed at the boundaries of the gen and in regions with a predominance of A–T pairs. It is shown, that for the occurrence of open states in the part of the gene that contains a small number of A–T pairs, a large amount of torque is required. When the torque is applied to a certain region of the gene, the probability of the formation of the open state depends on the content of A–T pairs in this region, the size of this region, and on the exposure time. For this mathematical model, open states zones can be closed when the torsion action stops. The simulation results showed that the values of the torsion moment required for the appearance of open states zones, in some cases, are close to experimentally measured (13–15 pN·nm).

Influence of a Single Deuterium Substitution for Protium on the Frequency Generation of Different-Size Bubbles in IFNA17

“…In comparison to the promoter and termination sequences, the coding region has the highest sum number of the nucleotides from the "Maximum" range (pχ 2 Yates = 0.0873, pχ 2 Yates < 0.0001, respectively), which reinforces OS and bubble generation in different groups foremost under E cr equals 0.250 (Figure 4, Table 1). At the same time, in the coding region, the maximum value of the nitrogenous bases was obtained, including in the "Minimum" range (pχ 2 Yates = 0.0002 and pχ 2 Yates < 0.0003 compared with the promoter and termination sequence, respectively; Figure 4, Table 2).…”

“…At the same time, in the coding region, the maximum value of the nitrogenous bases was obtained, including in the "Minimum" range (pχ 2 Yates = 0.0002 and pχ 2 Yates < 0.0003 compared with the promoter and termination sequence, respectively; Figure 4, Table 2). In addition, more nucleobases from these ranges were in the III part as opposed to the I part of the gene: pχ 2 Yates = 0.0014 (for "Maximum") and pχ 2 Yates < 0.0001 (for "Minimum"). It should be noted that the differences between AT fractions of the two ranges "Maximum" and "Minimum" in the coding region (39.9% and 44.5%) and the termination sequence (75.0% and 67.5%) were significant (pχ 2 Yates = 0.0004 and pχ 2 Yates < 0.0001).…”

“…The study of the reproduction mechanisms of genetic information makes it possible to expand the basic knowledge of biological systems and discover useful applications in biomedical research and biotechnology. The essential processes of any living organism are related to the configuration of the DNA macromolecule, and the generation of transcription bubbles during the transfer of genetic information substantially depends on the sequence of its nitrogenous bases [1][2][3][4]. It is well known that in order to copy genetic information, a transcription bubble appears, moving along the DNA strand [5].…”

“…Also, based on the angular model, it was found that the presence of deuterium in the chain of nucleotides can cause, depending on the value of the hydrogen bondbreaking energy, both an increase and a decrease in the probability of the occurrence of open states [23]. Moreover, the isotopic composition of the media, causing primarily a single 2 H/ 1 H replacement, affects the size of denaturation bubbles and the probability of their formation [24]. The angular model of DNA [25,26] makes it possible to take into consideration a quite wide range of external influences, such as the viscosity of the medium, the isotopic composition, and external forces [27][28][29][30].…”

Influence of Single Deuterium Replacement on Frequency of Hydrogen Bond Dissociation in IFNA17 under the Highest Critical Energy Range

“…The aim of this work is to study the effect of a single deuterium substitution at the frequency of hydrogen bond dissociation in IFNA17 in the range of the highest critical energies, based on the mechanical model of DNA [ 26 ], without simplifications and averaging [ 27 , 28 ].…”