DNA-metal(II) ion-phosphatidylcholine complexes: structure calculations and stability estimates by molecular mechanics

The structures and formation energies of nucleic acid-phospholipid complexes both in the absence and in the presence of Mg2+ ions were calculated taking double-stranded trinucleoside diphosphates NpNpN or heptanucleotides ApAp(NpNpN)pApA, composed of 64 possible combinations of genetic code, and phosphatidylcholine as model compounds. The dependence of intramolecular interactions on the primary structure of nucleic acid molecules and on the presence of a cationic bridge was revealed. The formation energies and structure of oligonucleotides were found by molecular mechanics calculations with the AMBER force field. The structures of phospholipid and MgCl2 molecules were calculated by the semiempirical PM3 method, white the energies of phospholipid-oligonucleotide complexes were calculated by the molecular mechanics method. Calculations of complexes were carried out with consideration of solvation effects. Considerable gain in the formation energy of triple complexes (13-14 kcal mol(-1)) is achieved due to the presence of the electroneutral metal bridge. A tendency toward increasing the stability of triple complexes containing guanosine- and cytidine-enriched triplets was revealed.