DNA-Polyamine Interactions: Insight from Molecular Dynamics Simulations on the Sequence-Specific Binding of Spermidine3+

DNA is a polyanion stabilized in vivo by positively charged counterions, including metal ions and small organic molecules, e.g., putrescine2+, spermidine3+, and spermine4+. In this chapter, after a brief review of previous studies on such DNA-counterion interactions, we focus the attention on the interactions between spermidine3+ and DNA. In this context, we present our original molecular dynamics simulation study to establish the specificity of the binding of polyamines to different nucleotide sequence motifs. Spermidine3+ molecules tend to be localized in the minor groove of the DNA double helix around the regions with AATT and ATAT nucleotide sequences. In the major groove, the polyamine does not bind to the AT-rich sequences, but instead localizes on the CG-region. The positioning of polyamines on the DNA surface also determines the DNA-DNA contacts due to the formation of polyamine cross-links. The cross-linking spermidine3+ molecules are localized parallel to the sugar-phosphate backbone of the double helix, neutralizing the negatively charged phosphate groups. The presented results are important for understanding the role of spermidine3+ in the biological functions of DNA and also have implications for possible technological applications.