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+)), Mg2+ and monovalent (Mf) ions wi th 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+), Mg2+, and M+ between t he 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 o f ions neutralizing the negative charge of DNA can vary in a broad range. T he GCMC simulations were used to provide appropriate conditions for subsequ ent 6 ns constant pressure and temperature MD simulations of DNA in a typic al 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 possib le to give an explanation why spermine molecules are usually not detected i n X-ray studies in spite of their high concentration in the preparatory sam ples used as the crystallizing agent. It appears that this flexible polyami ne molecule has several binding modes, interacting in fairly irregular mann er with different sites on DNA and showing no regular ordering in the DNA c rystals. Ions of Naf and Spm4+ compete with each other and with water molec ules in binding to bases in the minor groove and they influence the structu re of the DNA hydration shell in different ways. (C) 2001 Academic Press.