Jin Hongwei, Zheng Suxin, Wang Zhanli, Luo Cheng, Shen Jianhua, Jiang Hualiang, Zhang Liangren, Zhang Lihe
National Research Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, People's Republic of China.
J Mol Model. 2006 Sep;12(6):781-91. doi: 10.1007/s00894-005-0085-8. Epub 2006 Feb 1.
Some structural insights into the conformations of the isonucleosides containing duplexes have been provided. Unrestrained molecular-dynamics simulations on 18-mer duplexes with isonucleosides incorporated at the 3'-end or in the center of one strand have been carried out with explicit solvent under periodic boundary conditions using the AMBER force field and the particle mesh Ewald method. The Watson-Crick hydrogen-bonding patterns of the duplexes studied remained intact throughout the simulation. For the modified duplexes, the changes observed in the inter-base pair parameters and backbone torsional angles were primarily localized at the isonucleoside-inserted area. All five structures studied remained in the B-form family. The decreased stacking abilities indicated by the large changes in inter-base pair parameters and the large changes in backbones made the modified duplexes show a minor thermal destabilization in comparison with native DNA. The MM_PBSA method for estimating binding free energies on two complementary strands was used. The results showed that the binding free energies of isonucleoside-incorporated DNA duplexes were lower than the native DNA duplex, which is in good agreement with experimental observations.
已提供了一些关于含异核苷双链体构象的结构见解。使用AMBER力场和粒子网格埃瓦尔德方法，在周期性边界条件下，对在一条链的3'端或中心掺入异核苷的18聚体双链体进行了无约束分子动力学模拟，并使用了显式溶剂。所研究的双链体的沃森-克里克氢键模式在整个模拟过程中保持完整。对于修饰的双链体，在碱基对间参数和主链扭转角中观察到的变化主要局限于异核苷插入区域。所研究的所有五个结构都保留在B型家族中。碱基对间参数的大幅变化和主链的大幅变化表明堆积能力下降，这使得修饰的双链体与天然DNA相比显示出较小的热稳定性降低。使用MM_PBSA方法估算两条互补链上的结合自由能。结果表明，掺入异核苷的DNA双链体的结合自由能低于天然DNA双链体，这与实验观察结果高度一致。
