Wu Yuan-Yan, Zhang Zhong-Liang, Zhang Jin-Si, Zhu Xiao-Long, Tan Zhi-Jie
Department of Physics and Key Laboratory of Artificial Micro & Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
Department of Physics, School of Physics & Information Engineering, Jianghan University, Wuhan 430056, China.
Nucleic Acids Res. 2015 Jul 13;43(12):6156-65. doi: 10.1093/nar/gkv570. Epub 2015 May 27.
Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Co(NH3)6 (3+) (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive. However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become 'internal binding' into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit 'external binding' to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.
离子介导的相互作用对于核酸的结构和稳定性至关重要。最近的实验表明，多价离子诱导的双链（ds）RNA和DNA聚集可能强烈依赖于螺旋的拓扑性质，而在原子水平上对相关离子介导的相互作用仍缺乏了解。在这项工作中，我们通过原子分子动力学模拟直接计算了在六氨合钴（III）（Co-Hex）溶液中两条dsRNA之间以及两条dsDNA之间的平均力势（PMF）。我们的计算表明，在低[Co-Hex]浓度下，B-DNA之间以及A-RNA之间的PMF均为（强烈）排斥性。然而，在高[Co-Hex]浓度下，B-DNA之间的PMF具有强烈吸引力，而A-RNA之间以及A-DNA之间的PMF仍然是（微弱）排斥性的。微观分析表明，对于A-型螺旋，Co-Hex会“内部结合”到深的大沟中，因此无法在相邻螺旋之间形成明显的离子桥，而对于没有深沟的B-型螺旋，Co-Hex会表现出“外部结合”以强烈桥接相邻螺旋。此外，我们的进一步计算表明，在非常高的[Co-Hex]浓度下或当深大沟底部固定有一层水时，A-RNA之间的PMF也可能变得具有强烈吸引力。
