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Propagation of nonlinear conformational waves through the boundary dividing the double polynucleotide chain into two different homogeneous regions is investigated. Calculations are made in the frameworks of the DNA model which takes into account the difference in mass of nitrous bases and the difference in distances between sugar-phosphate chain and the centers of mass of bases which are connected with the chain by β-glycoside bond С₁-N. We consider different possible combinations of homogeneous regions placed on the right and on the left from the boundary, and we calculate the changes of the nonlinear wave velocity (v) and size (d) of the nonlinear waves due to overcoming the boundary.

Recently we have developed a new method for studying DNA based on ultrasound - induced cleavage of DNA sugar-phosphate backbone. Relative cleavage rates of the phosphodiester bonds in all 16 dinucleotides have been determined. The increased amount of data sampling (of more than 20 000 nucleotides) made it also possible to obtain cleavage rates in all 256 possible tetranucleotides. These values quantitatively characterize sequence effects on conformational dynamics of DNA sugar phosphate backbone. Same type of DNA heterogeneity have been discovered and studied using its chemical cleavage induced by various chemical agents and DNAse I. The presence of essential heterogeneity in structural properties of DNA might be a key for physical mapping of the genomes, i.e. determining the structural profiles being responsible for DNA recognition by gene expression regulation machinery.

In this paper we study the rotational oscillations of the nitrous bases forming a central pair in a short DNA fragment consisting of three base pairs. A simple mechanical analog of the fragment where the bases are imitated by pendulums and the interactions between pendulums — by springs, has been constructed. We derived Lagrangian of the model system and the nonlinear equations of motions. We found solutions in the homogeneous case when the fragment considered consists of identical base pairs: Adenine-Thymine (AT- pair) or Guanine-Cytosine (GC-pair). The trajectories of the model system in the configuration space were also constructed.

It is known that in the native state the DNA molecule always contains some amount of locally unwound regions, often called the open states of DNA. It is believed that these states play an important role in DNA-protein recognition and that the study of the open states dynamics may shed further light on the mechanisms of regulation of transcription and replication. In this paper we consider the effect of the thermostat on the movement of the open states in the artificial sequence consisting of four homogeneous regions. We construct the energetic profile of the sequence and investigate the trajectories of the movement of the open states under the action of a random force.

It is known that the internal mobility of DNA molecules plays an important role in the functioning of these molecules. This explains the great interest of researchers in studying the internal dynamics of DNA. Complexity, laboriousness and high cost of research in this field stimulate the search and creation of simpler physical analogues, convenient for simulating the various dynamic regimes possible in DNA. One of the directions of such a search is connected with the use of a mechanical analogue of DNA — a chain of coupled pendulums. In this model, pendulums imitate nitrous bases, horizontal thread on which pendulums are suspended, simulates a sugarphosphate chain, and gravitational field simulates a field induced by a second strand of DNA. Simplicity and visibility are the main advantages of the mechanical analogue. However, the model becomes too cumbersome in cases where it is necessary to simulate long (more than a thousand base pairs) DNA sequences. Another direction is associated with the use of an electronic analogue of the DNA molecule, which has no shortcomings of the mechanical model. In this paper, we investigate the possibility of using the Josephson line as an electronic analogue. We calculated the coefficients of the direct and indirect transformations for the simple case of a homogeneous, synthetic DNA, the sequence of which contains only adenines. The internal mobility of the DNA molecule was modeled by the sine-Gordon equation for angular vibrations of nitrous bases belonging to one of the two polynucleotide chains of DNA. The second polynucleotide chain was modeled as a certain average field in which these oscillations occur. We obtained the transformation, allowing the transition from DNA to an electronic analog in two ways. The first includes two stages: (1) the transition from DNA to the mechanical analogue (a chain of coupled pendulums) and (2) the transition from the mechanical analogue to the electronic one (the Josephson line). The second way is direct. It includes only one stage — a direct transition from DNA to the electronic analogue.

The functioning of DNA regulatory regions rely primarily on their physicochemical and structural properties but not on nucleotide sequences, i.e. ‘genetic text’. The formers are responsible for coding of DNA-protein interactions that govern various regulatory events. One of the characteristics is SIDD (Stress-Induced Duplex Destabilization) that quantify DNA duplex region propensity to melt under the imposed superhelical stress. The duplex property has been shown to participate in activity of various regulatory regions. Here we employ the SIDD model to calculate melting probability profiles for T7 bacteriophage promoter sequences. The genome is characterized by small size (approximately 40 thousand nucleotides) and temporal organization of expression: at the first stage of infection early T7 DNA region is transcribed by the host cell RNA polymerase, later on in life cycle phage-specific RNA polymerase performs transcription of class II and class III genes regions. Differential recognition of a particular group of promoters by the enzyme cannot be solely explained by their nucleotide sequences, because of, among other reasons, it is fairly similar among most the promoters. At the same time SIDD profiles obtained vary significantly and are clearly separated into groups corresponding to functional promoter classes of T7 DNA. For example, early promoters are affected by the same maximally destabilized DNA duplex region located at the varying region of a particular promoter. class II promoters lack substantially destabilized regions close to transcription start sites. Class III promoters, in contrast, demonstrate characteristic melting probability maxima located in the near-downstream region in all cases. Therefore, the apparent differences among the promoter groups with exceptional textual similarity (class II and class III differ by only few singular substitutions) were established. This confirms the major impact of DNA primary structure on the duplex parameter as well as a need for a broad genetic context consideration. The differences in melting probability profiles obtained using SIDD model alongside with other DNA physicochemical properties appears to be involved in differential promoter recognition by RNA polymerases.

In 2007 Kasman conducted a series of original computer experiments with sine-Gordon kinks moving along artificial DNA sequences. Two sequences were considered. Each consisted of two parts separated by a boundary. The left part of the first sequence contained repeating TTA triplets that encode leucines, and the right part contained repeating CGC triplets that encode arginines. In the second sequence, the left part contained repeating CTG triplets encoding leucines, and the right part contained repeating AGA triplets encoding arginines. When modeling the kink movement, an interesting effect was discovered. It turned out that the kink, moving in one of the sequences, stopped without reaching the end of the sequence, and then “bounced off” as if he had hit a wall. At the same time, the kink movement in the other sequence did not stop during the entire time of the experiment. In these computer experiments, however, a simple DNA model proposed by Salerno was used. It takes into account differences in the interactions of complementary bases within pairs, but does not take into account differences in the moments of inertia of nitrogenous bases and in the distances between the centers of mass of the bases and the sugar-phosphate chain. The question of whether the Kasman effect will continue with the use of more accurate DNA models is still open. In this paper, we investigate the Kasman effect on the basis of a more accurate DNA model that takes both of these differences into account. We obtained the energy profiles of Kasman's sequences and constructed the trajectories of the motion of kinks launched in these sequences with different initial values of the energy. The results of our investigations confirmed the existence of the Kasman effect, but only in a limited interval of initial values of the kink energy and with a certain direction of the kinks movement. In other cases, this effect did not observe. We discussed which of the studied sequences were energetically preferable for the excitation and propagation of kinks.

In this work, the problem of constructing an electronic analogue of heterogeneous DNA is solved with the help of the methods of mathematical modeling. Electronic analogs of that type, along with other physical models of living systems, are widely used as a tool for studying the dynamic and functional properties of these systems. The solution to the problem is based on an algorithm previously developed for homogeneous (synthetic) DNA and modified in such a way that it can be used for the case of inhomogeneous (native) DNA. The algorithm includes the following steps: selection of a model that simulates the internal mobility of DNA; construction of a transformation that allows you to move from the DNA model to its electronic analogue; search for conditions that provide an analogy of DNA equations and electronic analogue equations; calculation of the parameters of the equivalent electrical circuit. To describe inhomogeneous DNA, the model was chosen that is a system of discrete nonlinear differential equations simulating the angular deviations of nitrogenous bases, and Hamiltonian corresponding to these equations. The values of the coefficients in the model equations are completely determined by the dynamic parameters of the DNA molecule, including the moments of inertia of nitrous bases, the rigidity of the sugar-phosphate chain, and the constants characterizing the interactions between complementary bases in pairs. The inhomogeneous Josephson line was used as a basis for constructing an electronic model, the equivalent circuit of which contains four types of cells: A-, T-, G-, and C-cells. Each cell, in turn, consists of three elements: capacitance, inductance, and Josephson junction. It is important that the A-, T-, G- and C-cells of the Josephson line are arranged in a specific order, which is similar to the order of the nitrogenous bases (A, T, G and C) in the DNA sequence. The transition from DNA to an electronic analog was carried out with the help of the A-transformation which made it possible to calculate the values of the capacitance, inductance, and Josephson junction in the A-cells. The parameter values for the T-, G-, and C-cells of the equivalent electrical circuit were obtained from the conditions imposed on the coefficients of the model equations and providing an analogy between DNA and the electronic model.

To research dynamics of inhomogeneous polynucleotide DNA chain the Y-model with no dissipation term was used. Basing on this model using numerical methods calculations were carried out, which have shown the behaviour of nonlinear conformational excitation (kink), spreading along the inhomogeneous polynucleotide chain, consisting of two different homogeneous nucleotide sequences. As numerical analysis shows there are three ways of behaviour of the nonlinear kink excitation spreading along the DNA chain. After reaching the interface between two homogeneous sequences consisting of different types of bases kink can a) reflect, b) pass the interface with acceleration (increase its velocity), c) pass the interface with deceleration (decrease its velocity).

Here we demonstrate the results of kinetic modeilng of DNA double-strand breaks induction and repair and phosphorilated histone H2AX ($\gamma$-H2AX) and Rad51 foci formation in primary human fibroblasts exposed to low-LET ionizing radiation (IR). The model describes two major paths of DNA double-strand breaks repair: non-homologous end joining (NHEJ) and homologous recombination (HR) and considers interactions between DNA and several repair proteins (DNA-PKcs, ATM, Ku70/80, XRCC1, XRCC4, Rad51, RPA, etc.) using mass action equations and Michaelis–Menten kinetics. Experimental data on DNA rejoining kinetics and $\gamma$-H2AX and Rad51 foci formation in vicinity of double strand breaks in primary human fibroblasts exposed to low-LET IR with various dose rates and exposure times was utilized for training and statistical validation of the model.