Molecular dynamics simulation study of oriented polyamine‐ and Na‐DNA: Sequence specific interactions and effects on DNA structure

Molecular dynamics (MD) computer simulations have been carried out on four systems that correspond to an infinite array of parallel ordered B‐DNA, mimicking the state in oriented DNA fibers and also being relevant for crystals of B‐DNA oligonucleotides. The systems were all comprised of a periodical hexagonal cell with three identical DNA decamers, 15 water molecules per nucleotide, and counterions balancing the DNA charges. The sequence of the double helical DNA decamer was d(5′‐ATGCAGTCAG)×d(5′‐TGACTGCATC). The counterions were the two natural polyamines spermidine3+ (Spd3+) and putrescine2+ (Put2+), the synthetic polyamine diaminopropane2+ (DAP2+), and the simple monovalent cation Na+. This work compares the specific structures of the polyamine‐ and Na‐DNA systems and how they are affected by counterion interactions. It also describes sequence‐specific hydration and interaction of the cations with DNA. The local DNA structure is dependent on the nature of the counterion. Even the very similar polyamines, Put2+ and DAP2+, show clear differences in binding to DNA and in effect on hydration and local structure. Generally, the polyamines disorder the hydration of the DNA around their binding sites whereas Na+ being bound to DNA attracts and organizes water in its vicinity. Cation binding at the selected sites in the minor and in the major groove is compared for the different polyamines and Na+. We conclude that the synthetic polyamine (DAP2+) binds specifically to several structural and sequence‐specific motifs on B‐DNA, unlike the natural polyamines, Spd3+ and Put2+. This specificity of DAP2+ compared to the more dynamic behavior of Spd3+ and Put2+ may explain why the latter polyamines are naturally occurring in cells. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004