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.