Tag Archives: DNA

Standing on the shoulders of giants: James Watson, Francis Crick, Maurice Wilkins, Rosalind Franklin and the birth of molecular biology

T. V. Danylova1*, S. V. Komisarenko2

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
*e-mail: danilova_tv@ukr.net;
2Palladin Institute of Biochemistry, National Academy pf Sciences of Ukraine, Kyiv;
e-mail: svk@biochem.kiev.ua

Received: 14 April 2020; Accepted: 15 May 2020

In the 20th century, DNA became a magnet, attracting representatives of various sciences. Prominent researchers competed among themselves to discover the structure of DNA and to explain the mechanisms that determine our “natural fate”, i.e., our heredity. An American chemist, biochemist, chemical engineer Linus Pauling, a British physicist and molecular biologist Maurice Wilkins, a British chemist, biophysicist, and X-ray crystallographer Rosalind Franklin, an American geneticist, molecular biologist, zoologist James Watson, a British molecular biologist, biophysicist, and neuroscientist Francis Crick were among them. They searched for the scientific explanation for the enigma of life hidden in DNA. An accurate description of DNA double-helical structure belongs to James Watson and Francis Crick. However, the missing pieces of the puzzle were elaborated by Rosalind Franklin, who was not given enough credit for her dedicated scientific work. Unlike her, Francis Crick, James Watson, and Maurice Wilkins were awarded the Nobel Prize in Physiology or Medicine 1962 for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material. Whatever the DNA story is, it shows that all great scientific discoveries are not made from scratch. The immense number of people have contributed to the development of science and literally every researcher stands on the shoulders of giants, while the idea itself is in the air. The discovery of the structure of DNA became a cornerstone for the new scientific paradigm – biology acquired a molecular and biochemical basis.

Structural flexibility of canonical 2′-deoxyribonucleotides in DNA-like conformations

T. Yu. Nikolaienko1, L. A. Bulavin1, D. M. Hovorun1,2

1Taras Shevchenko Kyiv National University, Ukraine;
2Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
е-mail: tim_mail@ukr.net

Quantitative characteristics of structural flexibility of the DNA elementary monomer units – 5′-deoxycytidylic, 5′-thymidylic, 5′-deoxyadenylic and 5′-deoxyguanylic acid molecules – have been calculated with original methods. Root-mean-square deviations from equilibrium for all conformational parameters, caused by nuclei thermal or quantum zero-point vibrations, have been found to lie within 4°÷25° at 0 K and 7°÷50° at 298 K and corresponding relaxed force constants – within 1÷35 kcal/mol·rad-2. Their values have been found to be sensitive to the molecule’s conformation. It has been proven, that the torsion angle γ is the most rigid one whereas relaxed force constants for all other conformational variables are lower and comparable to each other. The data obtained could serve for development of structural-dynamical models of the DNA.

The 5′-deoxyadenylic acid molecule conformational capacity: quantum-mechanical investigation using density functional theory (DFT)

T. Yu. Nikolaienko1, L. A. Bulavin1, D. M. Hovorun1,2

1Taras Shevchenko Kyiv National University, Ukraine;
2Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
е-mail: tim_mail@ukr.net

Exhaustive conformational analysis of the 5′-deoxyadenylic acid molecule, has been carried out by the quantum-mechanical density functional theory method at the MP2/6-311++G(d,p) // DFT B3LYP/6-31G(d,p) theory level. As many as 726 of its conformations have been revealed with the relative gas phase Gibbs energies under standard­ conditions from 0 to 12.1 kcal/mole. It has been shown, that the energetically most favorable conformation has north sugar puckering and syn- orien­tation of the nitrogenous base and is stabilized by intramolecular OP1HP1∙∙∙N3 and O3′H∙∙∙OP hydrogen bonds. Four conformations have been shown to have their geometry similar to that of AI-DNA and four – of BI-DNA. One conformer of the 5′-deoxyadenylic acid molecule is similar to its sodium salt hexahydrate structure in crystalline state resolved by the X-ray diffraction method and taken from literature. It is shown that effective charges of C4′ and C5′ atoms are the most sensitive to the molecule conformation ones. The role of the intramolecular OH∙∙∙N hydrogen bonds in formation of the 5′-deoxyadenylic acid molecule structure has been demonstrated.

Conformational variety and physical properties of the 1,2-dideoxyribofuranose-5-phosphate, the model DNA monomer structural unit

T. Yu. Nikolaienko1, L. A. Bulavin1, D. M. Hovorun1,2, O. O. Missura1

1Taras Shevchenko Kyiv National University, Ukraine;
2Institute of Molecular Biology and Genetics,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: tim_mail@ukr.net

The results of exhaustive quantum-mechani­cal conformational analysis of 1,2-dideoxyribofuranose-5-phosphate molecule, the model DNA backbone structural unit, are presented. As many as 282 conformations with the relative Gibbs energies from 0 to 8.9 kcal/mole have been obtained at the MP2/cc-pVTZ // DFT B3LYP/cc-pVTZ theory level. Among them seven structures are similar to those of the DNA backbone in its AI, BI and ZII forms, while the B-DNA-like conformation has the lowest Gibbs energy (ΔG = 3.3 kcal/mole). It is shown that the relaxed force constants values­ for conformational parameters of all DNA-like conformations satisfy inequality Kγ > Kα′ > Kε > Kβ.

Estimation of the ROS in the presence of biologically active substances by porous silicon fluorescence

V. B. Shevchenko1, O. I. Dacenko1, O. V. Shablykin2, T. V. Osadchuk2,
A. M. Lyakhov2, Y. V. Pivovarenko3, V. A. Makara1,3

1Taras Shevchenko Kyiv National University, Ukraine;
e-mail: shevchenko@univ.kiev.ua;
2Institute of Bioorganic Chemistry and Petroleum Chemistry,
National Academy of Sciences of Ukraine;
3STC Physico-Chemical Center of Materials Science
of Taras Shevchenko Kyiv National University and NAS of Ukraine

The fluorescence spectra of the porous silicon modified by water solutions of biologically active materials and materials of biological origin are recorded as well as the fluorescence spectra of the porous silicon modified by lecithin monolayers grown on the surface of water solutions of the biologically active materials. The analysis of the obtained spectra made it possible to conclude on the effect of the studied materials on the content of ROS.

The effect of chlorination of nucleotide bases on the conformational properties of thymidine monophosphate

T. M. Mukhina, T. Yu. Nikolaienko

Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: MukhinaTanyaM@gmail.com; tim_mail@ukr.net

Recent studies on Escherichia coli bacteria cultivation, in which DNA thymine was replaced with 5-chlorouracil have refreshed the problem of understanding the changes to physical properties of DNA monomers resultant from chemical modifications. These studies have shown that the replacement did not affect the normal activities and division of the bacteria, but has significantly reduced its life span. In this paper a comparative analysis was carried out by the methods of computational experiment of a set of 687 possible conformers of natural monomeric DNA unit (2′-deoxyribonucleotide thymidine monophosphate) and 660 conformers of 5-chloro-2′-deoxyuridine monophosphate – a similar molecules in which the natural nitrogenous base thymine is substituted with 5-chlorouracil. Structures of stable conformers of the modified deoxyribonucleotide have been obtained and physical factors, which determine their variation from the conformers of the unmodified molecule have been analyzed. A comparative analysis of the elastic properties of conformers­ of investigated molecules and non-covalent interactions present in them was conducted. The results can be used for planning experiments on synthesis of artificial DNA suitable for incorporation into living organisms.