[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.

[Possible configuration of dimers of Gua-Cyt bases. Computation by molecular mechanic models and density functional theory]. / Vozmozhnye konfiguratsii dimerov osnovanii DNK Gua-Cyt. Raschety metodami mekhaniki i teorii funktsional plotnosti.

The energies of interactions between guanine and cytosine in various mutual positions were calculated by the methods of molecular mechanics with refined atom-atom potential functions and the quantum mechanics theory of density functional. Both methods indicate three types of mutual positions of bases in local energy minima. These types correspond to (1) nearly coplanar base positions with intermolecular hydrogen bond formation (base pairing); (2) arrangements of two bases in nearly parallel planes one above another (base stacking); and (3) nearly perpendicular positions of base planes. According to the calculations, the global energy minimum corresponds to the Watson-Crick base pair with three hydrogen bonds. A specific feature of the pair is a transition from many positions of type (2) to positions of type (1) without any energy barrier. This feature is revealed by both methods. Another special feature of this pair is a deviation, for most of mutual base positions, of the amine group atoms from the ring plane, the deviation being more pronounced for Gua. These features are important for understanding the conformational behavior of DNA fragments and the RNA structure.

[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.

[Interactions between nucleic acid bases. New parameters of potential functions and energy minima]. / Vzaimodeistviia mezhdu osnovaniiami nukleinovykh kislot. Novye parametry potentsialov i novye minimumy énergii.

The parameters of atom-atom potential functions suggested by one of the authors in 1979-1986 were slightly changed. The changes were performed to achieve a better agreement with experimental data of interaction energy values in global minima and hydrogen bond lengths. These changes resulted in better accord with experimental values of distances between the layers in DNA monomer crystals and between the base pairs in oligonucleotide duplexes. The refined potential functions were used to calculate the energy of interactions between nucleic acid bases in various mutual positions. The calculations revealed a few types of mutual base arrangements in minima of interaction energy for each pairwise base combination. A new type of minima was found, which correspond to a nearly perpendicular arrangement of base rings and the formation of the intermolecular hydrogen bond.