Study of mechanisms of some caffeine biological effects via computer simulation of its interactions with DNA fragments

To approach atomic level mechanisms of caffeine biological activity, molecular mechanics computations of interactions between caffeine molecule and DNA duplex fragments, containing four nucleotide pairs, have been performed. The calculations reveal a set of energy minima referring to rather compact caffeine arrangement in both major and minor grooves of the helix. The set includes the minima correspondent to the H-bond formation by any of the three proton acceptor atoms of caffeine with any of the three amino groups of DNA bases. Both H-bonded to caffeine nucleotides and some neighbor nucleotides of both chains contribute substantially to the total interaction energy. A possibility of caffeine complexation with DNA duplex suggests a possible mechanism of caffeine influence on DNA functioning via its competition with other ligands.