Binding Sites of the Polyamines Putrescine, Cadaverine, Spermidine and Spermine on A- and B-DNA Located by Simulated Annealing

Abstract

Molecular dynamics simulations with simulated annealing are performed on polyamine-DNA systems in order to determine the binding sites of putrescine, cadaverine, spermidine and spermine on A- and B-DNA. The simulations either contain no additional counterions or sufficient Na+ ions, together with the charge on the polyamine, to provide 73% neutralisation of the charges on the DNA phosphates. The stabilisation energies of the complexes indicate that all four polyamines should stabilise A-DNA in preference to B-DNA, which is in agreement with experiment in the case of spermine and spermidine, but not in the case of putrescine or cadaverine. The major groove is the preferred binding site on A-DNA of all the polyamines. Putrescine and cadaverine tend to bind to the sugar-phosphate backbone of B-DNA, whereas spermidine and spermine occupy more varied sites, including binding along the backbone and bridging both the major and minor grooves.

Influence of cationic molecules on the hairpin to duplex equilibria of self-complementary DNA and RNA oligonucleotides

“…Alkali and alkali earth metal ions preferentially bind to nucleotide phosphates, and the polyamines are reported to bind in the duplex grooves (46–48). Moreover, basic amino acid residues in proteins often participate in the DNA binding through the electrostatic interaction, e.g.…”

Polyamine-dependent gene expression

“…The major groove of A-DNA is the site preferred by all polyamines. In B-DNA putrescine prefers the sugar-phosphate backbone as the binding site, whereas spermidine and spermine bind along the backbone and in the major or minor groove [30]. Preferential binding sites for each polyamine have been proposed based on spectral analysis.…”

Antisense and Antigene Inhibition of Gene Expression by Cell-Permeable Oligonucleotide–Oligospermine Conjugates

“…While free spermine can bind to both B-form and A-form helical structures, 20,21 its interactions with the A-form helix are more energetically favorable. 20 Accordingly, oligospermine conjugation increased binding affinity toward RNA target strands more than DNA target strands (0.7 °C/spermine for RNA vs. 0.3 °C/spermine for DNA; Figure S5 D,E). This suggests that the stabilizing effect conferred by oligospermine conjugation is not simply due to charge neutralization, but contains a structural component.…”