Sen S, Nilsson L
Contribution from the Department of Bioscience at NOVUM, Center for Structural Biochemistry, Karolinska Institutet, S-14157, Huddinge, Sweden.
J Am Chem Soc. 2001 Aug 1;123(30):7414-22. doi: 10.1021/ja0032632.
MD simulations of homomorphous single-stranded PNA, DNA, and RNA with the same base sequence have been performed in aqueous solvent. For each strand two separate simulations were performed starting from a (i) helical conformation and (ii) random coiled state. Comparisons of the simulations with the single-stranded helices (case i) show that the differences in the covalent nature of the backbones cause significant differences in the structural and dynamical properties of the strands. It is found that the PNA strand maintains its nice base-stacked initial helical structure throughout the 1.5-ns MD simulation at 300 K, while DNA/RNA show relatively larger fluctuations in the structures with a few local unstacking events during -ns MD simulation each. It seems that the weak physical coupling between the bases and the backbone in PNA causes a loss of correlation between the dynamics of the bases and the backbone compared to the DNA/RNA and helps maintain the base-stacked helical conformation. The global flexibility of a single-stranded PNA helix was also found to be lowest, while RNA appears to be the most flexible single-stranded helix. The sugar pucker of several nucleotides in single-stranded DNA and RNA was found to adopt both C2'-endo and C3'-endo conformations for significant times. This effect is more pronounced for single strands in completely coiled states. The simulations with single-stranded coils as the initial structure also indicate that a PNA can adopt a more compact globular structure, while DNA/RNA of the same size adopts a more extended coil structure. This allows even a short PNA in the coiled state to form a significantly stable nonsequentially base-stacked globular structure in solution. Due to the hydrophobic nature of the PNA backbone, it interacts with surrounding water rather weakly compared to DNA/RNA.
在水性溶剂中对具有相同碱基序列的同形单链肽核酸（PNA）、DNA和RNA进行了分子动力学（MD）模拟。对于每条链，从（i）螺旋构象和（ii）无规卷曲状态开始进行了两个独立的模拟。与单链螺旋（情况i）的模拟比较表明，主链共价性质的差异导致链的结构和动力学性质存在显著差异。结果发现，在300 K下进行的1.5纳秒MD模拟过程中，PNA链始终保持其良好的碱基堆积初始螺旋结构，而DNA/RNA在各自的纳秒MD模拟过程中结构波动相对较大，出现了一些局部解堆积事件。与DNA/RNA相比，PNA中碱基与主链之间较弱的物理耦合导致碱基与主链动力学之间的相关性丧失，并有助于维持碱基堆积的螺旋构象。还发现单链PNA螺旋的整体柔性最低，而RNA似乎是最柔性的单链螺旋。发现单链DNA和RNA中几个核苷酸的糖环构象在相当长的时间内同时采用C2'-内向和C3'-内向构象。这种效应在完全卷曲状态的单链中更为明显。以单链卷曲作为初始结构的模拟还表明，PNA可以采用更紧凑的球状结构，而相同大小的DNA/RNA则采用更伸展的卷曲结构。这使得处于卷曲状态的短PNA即使在溶液中也能形成显著稳定的非顺序碱基堆积球状结构。由于PNA主链的疏水性，与DNA/RNA相比，它与周围水的相互作用较弱。
