Korolev Nikolay, Lyubartsev Alexander P, Laaksonen Aatto, Nordenskiöld Lars
School of Biological Sciences, NTU - Nanyang Technological University, No. 1 Nanyang Walk, Blk. 5, Level 3, Singapore 637616.
Biopolymers. 2004 Apr 5;73(5):542-55. doi: 10.1002/bip.10583.
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)xd(5'-TGACTGCATC). The counterions were the two natural polyamines spermidine(3+) (Spd(3+)) and putrescine(2+) (Put(2+)), the synthetic polyamine diaminopropane(2+) (DAP(2+)), 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, Put(2+) and DAP(2+), 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 (DAP(2+)) binds specifically to several structural and sequence-specific motifs on B-DNA, unlike the natural polyamines, Spd(3+) and Put(2+). This specificity of DAP(2+) compared to the more dynamic behavior of Spd(3+) and Put(2+) may explain why the latter polyamines are naturally occurring in cells.
已对四个系统进行了分子动力学（MD）计算机模拟，这些系统对应于无限阵列的平行有序B-DNA，模拟了定向DNA纤维中的状态，也与B-DNA寡核苷酸晶体相关。这些系统均由一个周期性六边形单元组成，其中包含三个相同的DNA十聚体、每个核苷酸15个水分子以及平衡DNA电荷的抗衡离子。双螺旋DNA十聚体的序列为d(5'-ATGCAGTCAG)xd(5'-TGACTGCATC)。抗衡离子为两种天然多胺亚精胺(3+)（Spd(3+)）和腐胺(2+)（Put(2+)）、合成多胺二氨基丙烷(2+)（DAP(2+)）以及简单的单价阳离子Na(+)。这项工作比较了多胺-DNA系统和Na-DNA系统的特定结构以及它们如何受到抗衡离子相互作用的影响。它还描述了阳离子与DNA的序列特异性水合作用和相互作用。局部DNA结构取决于抗衡离子的性质。即使是非常相似的多胺Put(2+)和DAP(2+)，在与DNA结合以及对水合作用和局部结构的影响方面也表现出明显差异。一般来说，多胺会扰乱其结合位点周围DNA的水合作用，而与DNA结合的Na(+)会吸引并组织其附近的水。比较了不同多胺和Na(+)在小沟和大沟中选定位点的阳离子结合情况。我们得出结论，与天然多胺Spd(3+)和Put(2+)不同，合成多胺（DAP(2+)）特异性结合于B-DNA上的几个结构和序列特异性基序。与Spd(3+)和Put(2+)更具动态性的行为相比，DAP(2+)的这种特异性可能解释了为什么后两种多胺天然存在于细胞中。
