Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments.

Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.

[Analysis of Conformational Features of Watson-Crick Duplex Fragments by Molecular Mechanics and Quantum Mechanics Methods].

It is generally accepted that the important characteristic features of the Watson-Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three-dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the limits typical for the corresponding family. We observe that popular functionals in density functional theory calculations lead to the overestimated distances between base pairs, while MP2 computations and the newer complex functionals produce the structures that have too close atom-atom contacts. A detailed study of some complementary desoxydinucleoside monophosphate complexes with Na-ions highlights the existence of several energy minima corresponding to BI-conformations, in other words, the complexity of the relief pattern of the potential energy surface of complementary desoxydinucleoside monophosphate complexes. This accounts for variability of conformational parameters of duplex fragments with the same base sequence. Popular molecular mechanics force fields AMBER and CHARMM reproduce most of the conformational characteristics of desoxydinucleoside monophosphates and their complementary complexes with Na-ions but fail to reproduce some details of the dependence of the Watson-Crick duplex conformation on the nucleotide sequence.

[Interactions of caffeine with DNA double helix fragments. Molecular mechanics simulation].

Calculations of the energy of interaction between the caffeine molecule and DNA double helix fragment of four complementary pairs have been performed by the molecular mechanics method. The calculations demonstrate the existence of energy minima corresponding to the caffeine molecule position in both wide and narrow grooves. Each of three proton acceptor atoms of caffeine is able to form hydrogen bond with each of three amino groups of DNA bases. The interactions of caffeine with both hydrogen bonded nucleotide and other nucleotides of the two strands contribute considerably to the total energy. The substantial contribution of interactions of caffeine with other than H-bonded nucleotides results in a rather close packing of atom groups in possible DNA-caffeine complexes. The mechanisms of influence of caffeine on interactions of DNA with other biologically active compounds are discussed.

[Interaction of caffeine with basic nucleic acids my a molecular mechanic method]. / Issledovanie vzaimodeistviia kofeina s osnovaniiami nukleinovykh kislot metodom molekuliarnoi mekhaniki.

To understand some aspects of the biological action of caffeine (CAF), the interaction energies for various mutual positions of CAF and DNA bases or basepairs were calculated. Three types of mutual CAF-base (CAF-basepair) arrangements corresponding to the minima of interaction energy were revealed. One type of minima correspond to the stacking arrangement of molecules. This type is important for interactions of CAF with DNA monomers and single-stranded fragments. The other two types of minima correspond to the formation of intermolecular hydrogen bonds. Some of these minima may occur during the interaction of CAF with the double helix. One of these types corresponds to the nearly in-plane position of molecules. The other type of minima correspond to the nearly perpendicular arrangement of molecule planes. The minima of the last type are supposed to be the most important for the interaction of CAF with the DNA duplex, and interaction energies for this type of minima have the most negative values.

Polypeptide composition of submitochondrial fractions of normal liver tissue and Zajdela hepatoma.

The polypeptide composition of liver and Zajdela hepatoma mitochondria is compared. Polypeptides of mitochondria and submitochondrial fractions (the outer and the inner mitochondrial membranes, the intermembrane and the matrix spaces of mitochondria) were separated by electrophoresis in polyacrylamide gel. The percentage content of each polypeptide was evaluated after scanning gels using a differential spectrophotometer-densitometer. Significant changes of several proteins of the hepatoma mitochondria and submitochondrial fractions as compared with normal liver preparations have been found.

Changes in phospholipids during the cell cycle of myxomycete Physarum polycephalum.

The rate of 32Pi incorporation into the main membrane phospholipid fractions, i.e. phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), as well as their contents in the cells during synchronous growth of the myxomycete, Physarum polycephalum, have been studied. It has been found that both the phospholipid levels and the rates of 32Pi incorporation increase during the S phase till the early G2 phase, remain nearly constant during the G2 phase and fall to the initial level at the end of the G2 phase and in mitosis. It has been revealed that the rate of 32Pi incorporation into PC is very low compared to PE and PI, in spite of the fact that the PC level is the highest. The possible reasons of this phenomenon are discussed.

[Metabolite level from energy metabolism in Escherichia coli cells during growth on various substrates]. / Soderzhanie metabolitov énergeticheskogo obmena v kletkakh Escherichia coli pri roste na raznykh substratakh.

In the present work, an attempt has been made to analyse some parameters of the intracellular energy metabolism and to determine whether they are related to the cell growth rate. The authors measured intracellular concentrations of adenine nucleotides, the content of glycogen, an energy "depot" of glucose, the rate of its synthesis, and the content of glutathione which specifies the redox state in the cytoplasm of E. coli cells upon continuous cultivation on a minimal nutrient medium containing various carbon sources (glucose, glycerol, lactate, and acetate). It was found that the specific contents of adenine nucleotides and reduced glutathione were independent of the cell growth rate. Based on the results obtained, it is assumed that a possible reason for changes in the duration of the sell cycle of the bacteria cultured on different substrates is an alteration in the content of reserve carbohydrates.

[Effect of the respiratory chain redox state on mitochondrial membrane permeability for K+ ions]. / Vliianie redoks-sostoianiia dykhatel'noi tsepi na pronitsaemost' membrany mitokhondrii dlia ionov kaliia.

Transport of Pi into mitochondrial matrix induces K+-permeability of the membranes, which results from the addition of DNP. This induction of K+ efflux is eliminated by some agents causing the respiratory chain reduction (e.g. succinate, rotenone, antimycin A). It was shown that the abolition of the membrane potential is not sufficient for K+ efflux induction. The latter process is necessary for the energy-linked formation of the K+-transporting system. The lipid fraction containing lecithin and monophosphoinositol was extracted from the mitochondria after preincubation with Pi. The artificial bilayer membranes formed from these lipids are permeable for K+.