Physical Chemistry Department, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland.
J Mol Model. 2013 Aug;19(8):3339-49. doi: 10.1007/s00894-013-1859-z. Epub 2013 May 15.
The structural and energetic properties of native and oxidized telomeric complexes were defined by means of molecular dynamic (MD) simulations. As a starting point, the experimental conformation of B-DNA d(GpTpTpApGpGpGpTpTpApGpGpG) oligomer bound to human protein telomeric repeat binding factor 1 (TRF1) was used. The influence on the stability of the telomeric complex of the presence of 8-oxoguanine (8oxoG) in the central telomeric triad (CTT) was estimated based on trajectories collected during 130 ns MD runs. The data obtained indicate that the system analyzed is highly sensitive to the presence of oxidative damage in the CTT of the B-DNA telomeric sequence. The most important changes were observed in the immediate vicinity of the 8-oxoguanine molecule. The significantly higher mobility of arginine 425 interacting directly with the oxidized guanine molecule has a large influence on the structural, dynamic and energetic properties of neighboring amino acids. Local changes observed for individual hydrogen bonded interactions localized in the major groove of B-DNA also have significant impact on the properties of hydrophobic clusters, which are the second type of force responsible for stability of the studied bio-system. All the changes reported in detail here unambiguously indicate a significant decrease in telomer binding affinity after oxidation.
通过分子动力学（MD）模拟，确定了天然和氧化端粒复合物的结构和能量特性。作为起点，使用与人类蛋白端粒重复结合因子 1（TRF1）结合的 B-DNA d(GpTpTpApGpGpGpTpTpApGpGpG)寡聚物的实验构象。根据 130ns MD 运行过程中收集的轨迹，估计了中央端粒三联体（CTT）中 8-氧鸟嘌呤（8oxoG）存在对端粒复合物稳定性的影响。所得数据表明，所分析的系统对 B-DNA 端粒序列 CTT 中氧化损伤的存在非常敏感。在 8-氧鸟嘌呤分子的直接附近观察到最重要的变化。与氧化的鸟嘌呤分子直接相互作用的精氨酸 425 的显著更高的流动性对邻近氨基酸的结构、动态和能量特性有很大影响。在 B-DNA 大沟中局部化的单个氢键相互作用中观察到的局部变化也对疏水区簇的特性有重大影响，疏水区簇是负责研究生物系统稳定性的第二类力。这里详细报告的所有变化都明确表明，氧化后端粒结合亲和力显著降低。
