On the competition between water, sodium ions, and spermine in binding to DNA:: a molecular dynamics computer simulation study

The interaction of DNA with the polyamine spermine(4+)(Spm(4+)), sodium ions, and water molecules has been studied using molecular dynamics computer simulations in a system modeling a DNA crystal. The simulation model consisted of three B-DNA decamers in a periodic hexagonal cell, containing 1200 water molecules, 8 Spm(4+), 32 Na+, and 4 Cl- ions. The present paper gives a more detailed account of a recently published report of this system and compares results on this mixed Spm(4+)/Na+-cation system with an molecular dynamics simulation carried out for the same DNA decamer under similar conditions with only sodium counterions (Korolev et al., 2001, J. Mol. Biol. 308:907). The presence of Spm(4+) makes significant influence on the DNA hydration and on the interaction of the sodium ions with DNA. Spermine pushes water molecules out of the minor groove, whereas Na+ attracts and organizes water around DNA. The major binding site of the Spm(4+) amino groups and the Na+ ions is the phosphate group of DNA. The flexible polyamine spermine displays a high presence in the minor groove but does not form long-lived and structurally defined complexes. Sodium ions compete with Spm(4+) for binding to the DNA bases in the minor groove. Sodium ions also have several strong binding sites in the major groove. The ability of water molecules, Spm(4+), and Na4+ to modulate the local structure of the DNA double helix is discussed.