Conformational implications of some nucleotide sequences

The conformational properties of some nucleotide sequences result in their ability to bind specifically some ligands or tobe recognized by specific proteins. In order to investigate the dependence of conformational behavior of the DNA duplex on nucleotide sequence, we analyzed the interaction energy of nucleic acid bases as a function of conformational parameters and base sequence. Extended regions of minimum energy values were found for different sequences. Although these regions (valleys) largely overlap, each one shows specificity for a particular sequence. This suggests that a specific pathway of changes in conformational parameters exists for each sequence. the changes may be accompanied by considerable shifts (2–3 Å) of the atom positions and an only slight variation (1–2 kcal/mol) of energy. Even small shifts in other directions can cause a drastic energy increase. For some nucleotide sequences, the energetically preferable conformations are the B-like ones (e.g., ApA, TpA), whereas for others the A-like ones are preferable (e.g., GpG, ApT). IN general, Pyr-Pur sequences have a tendency to a larger τ and smaller H and D than Pur-Pyr sequences. A large body of experimental data on nucleic acid structure in fibers and in solutions can be explained by results obtained.     

Simulation of intermolecular and intramolecular interactions of nucleic acid subunits by means of atom–atom potential functions

Atom–atom potential functions for calculation of nonbonded interaction energies of nucleic acids are proposed. Quantitative reliability of the obtained results is checked by using the calculations of intermolecular interaction energy in crystals. Based on the calculations of the interaction energy of the nucleic acid bases the molecular mechanisms of spontaneous mutations are suggested.     

DFT study of polymorphism of the DNA double helix at the level of dinucleoside monophosphates

We apply DFT calculations to deoxydinucleoside monophosphates (dDMPs) which represent minimal fragments of the DNA chain to study the molecular basis of stability of the DNA duplex, the origin of its polymorphism and conformational heterogeneity. In this work, we continue our previous studies of dDMPs where we detected internal energy minima corresponding to the “classical” B conformation (BI‐form), which is the dominant form in the crystals of oligonucleotide duplexes. We obtained BI local energy minima for all existing base sequences of dDMPs. In the present study, we extend our analysis to other families of DNA conformations, successfully identifying A, BI, and BII energy minima for all dDMP sequences. These conformations demonstrate distinct differences in sugar ring puckering, but similar sequence‐dependent base arrangements. Internal energies of BI and BII conformers are close to each other for nearly all the base sequences. The dGpdG, dTpdG, and dCpdA dDMPs slightly favor the BII conformation, which agrees with these sequences being more frequently experimentally encountered in the BII form. We have found BII‐like structures of dDMPs for the base sequences both existing in crystals in BII conformation and those not yet encountered in crystals till now. On the other hand, we failed to obtain dDMP energy minima corresponding to the Z family of DNA conformations, thus giving us the ground to conclude that these conformations are stabilized in both crystals and solutions by external factors, presumably by interactions with various components of the media. Overall the accumulated computational data demonstrate that the A, BI, and BII families of DNA conformations originate from the corresponding local energy minimum conformations of dDMPs, thus determining structural stability of a single DNA strand during the processes of unwinding and rewinding of DNA. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2548–2559, 2010     

Computational investigation of the role of hydration in nucleic acid structure and function

The results of the Monte Carlo Metropolis simulation of water structure and of the hydration of nucleic acid fragments, complementary base pairs and mispairs, base pair stacks, and duplex fragments have been summarized. Systematic investigations suggest some general conclusions: (1) the hydration shell structure of the major and minor grooves of the duplex depends significantly on DNA conformation (or stack configuration) and nucleotide sequence, while global hydration characteristics (average energy, the number of water–water and water–base H-bonds) are only slightly dependent on these factors, (2) hydration economy takes place in the B–A transition due to an increase of the number of water molecules forming hydrogen bonds with two or more atoms of bases (water bridging), and (3) the hydration of the duplex could contribute to nucleic acid functioning via water-bridged mispair formation and stabilization of specific conformations.     

Monte Carlo study of three-dimensional organization of water molecules around DNA fragments

Interactions with water molecules are important for the stabilization of three-dimensional structures of nucleic acids and for their functioning. The first hydration shells of macromolecules can be considered as structural parts of nucleic acid. We performed a Monte Carlo study of systems containing a nucleic acid base or base pair with water molecules using improved potential functions. These potential functions enable experimental data on both single base–single water interaction energies and enthalpies of base hydration to be reproduced. Hydration shell structures of base pairs are dependent on the pair geometry. Structural elements of hydration shells can contribute to the pair stability and hence to the probability of mispair formation during nucleic acid biosynthesis. The distribution of water molecules around bases and base pairs is essentially nonhomogeneous.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002).     

Backward electron transport in photosystem 2 reaction center and temperature dependence of delayed luminescence characteristics

The temperature dependence of parameters of light-induced changes in millisecond delayed luminescence (half-width of the maximum, maximal and steady-state luminescence intensity) is studied within the temperature range from -23 to 45 degrees C in leaf segments of Chinese rose (Hibiscus rosa sinensis). Delayed luminescence (DL) is induced and registered by a homemade setup based on a Lewis-Kasha-type phosphoroscope. The temperature dependence of steady-state luminescence intensity is shown to have two maxima, at -10 and 35 degrees C. At room temperatures, the steady-state value of luminescence intensity is minimal, and its value correlates with the temperature tolerance of the plant. Depending on cooling and heating regimes, the DL steady-state value vs. temperature curves is found to be different. We suppose this effect to be caused by temperature-induced destructive changes in the structure of photosystem 2 reaction centre and probably by salting out.     

Caffeine interactions with nucleic acids. Molecular mechanics calculations of model systems for explanation of mechanisms of biological actions

To understand the molecular mechanisms of the influence of caffeine (CAF) on DNA functioning, molecular mechanics calculations of the interaction energy of CAF with nucleic acid bases and base pairs have been performed. The calculations reveal three types of mutual CAF–base (and CAF–base pair) arrangements corresponding to minima of the interaction energy. Besides well-known stacking mutual positions of the molecules, two other types of arrangements are revealed and studied. One of these arrangements corresponds to the nearly in-plane position of CAF and base (or base pair) and the formation of a single hydrogen bond. Another type of minimum corresponds to nearly perpendicular arrangements of the molecular planes and the formation of intermolecular hydrogen bonds. These two arrangements are possible both for individual nucleic acid monomers and for DNA duplexes. The calculations suggest the molecular mechanisms of the influence of CAF on DNA interactions with other biologically active molecules.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 20002).