Spermine: an “invisible” component in the crystals of B-DNA. A grand canonical Monte Carlo and molecular dynamics simulation study

The association of spermine 4+ (Spm 4+), Mg 2+ and monovalent (M +) ions with DNA in crystal form, have been studied using grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) computer simulations. GCMC calculations were used to calculate the distribution of Spm 4+, Mg 2+, and M + between the equilibrating solvent and the DNA crystal under conditions mimicking the crystal-growing protocols reported in a number of recent X-ray diffraction studies of DNA oligomers. The GCMC simulations show that the composition of ions neutralizing the negative charge of DNA can vary in a broad range. The GCMC simulations were used to provide appropriate conditions for subsequent 6 ns constant pressure and temperature MD simulations of DNA in a typical crystalline environment consisting of three DNA double helix decamers in a periodic hexagonal cell, containing 1200 water molecules, eight Spm 4+, 32 Na + and four Cl − ions. Based on the simulation results, it seems possible to give an explanation why spermine molecules are usually not detected in X-ray studies in spite of their high concentration in the preparatory samples used as the crystallizing agent. It appears that this flexible polyamine molecule has several binding modes, interacting in fairly irregular manner with different sites on DNA and showing no regular ordering in the DNA crystals. Ions of Na + and Spm 4+ compete with each other and with water molecules in binding to bases in the minor groove and they influence the structure of the DNA hydration shell in different ways.