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).     

Database of amino acid-nucleotide contacts in contacts in DNA-homeodomain protein

The analysis of amino acid-nucleotide contacts in interfaces of the protein-DNA complexes, intended to find consistencies in the protein-DNA recognition, is a complex problem that requires an analysis of the physicochemical characteristics of these contacts and the positions of the participating amino acids and nucleotides in the chains of the protein and the DNA, respectively, as well as conservatism of these contacts. Thus, those heterogeneous data should be systematized. For this purpose we have developed a database of amino acid-nucleotide contacts ANTPC (Amino acid Nucleotide Type Position Conservation) following the archetypal example of the proteins in the homeodomain family. We show that it can be used to compare and classify the interfaces of the protein-DNA complexes.