石墨烯纳米孔定位和识别DNA损伤位点的分子模拟研究

项目名称： 石墨烯纳米孔定位和识别DNA损伤位点的分子模拟研究

项目编号： No.21505134

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 吕闻凭

作者单位： 中国科学院大连化学物理研究所

项目金额： 21万元

中文摘要： 纳米孔是新一代基因测序技术，主要根据DNA链在纳米孔内输运时引起的离子电流阻塞来读取基因信息。受损DNA具有与正常DNA不同的物理结构和化学性质，可以对纳米孔内的离子电流产生特异性阻塞效果。但是，定位和识别DNA的损伤位点还需要突破传统纳米孔的低空间分辨率限制，提取各损伤位点在纳米孔内对应的特征离子电流信号。本项目拟利用石墨烯纳米孔的单原子厚度所具备的单碱基分辨潜力，通过模拟计算，在原子、分子尺度上研究石墨烯纳米孔对DNA链上损伤位点的识别和定位能力。重点从受损DNA 分子在石墨烯纳米孔内阻塞离子流的分子机制着手，计算孔内各分子间相互作用、离子输运自由能变化等控制离子阻塞效果的物理化学参量，探讨离子电流阻塞对DNA固有结构差异的敏感性，预测DNA输运过程中损伤位点诱导的阻塞离子电流信号，分析不同类型的DNA损伤引起的特征离子电流，为进一步提高纳米孔实验的分辨率提供理论支撑。

中文关键词： 芯片电泳；纳米孔；DNA损伤；单分子检测；分子模拟

英文摘要： Nanopore sequencing, as the next generation sequencing technology, can read the gene information from the ionic current blockage induced by the transport of a single DNA molecule in pore. The damaged DNA and unmodified DNA have discrepant physical structures and chemical properties. These differences could induce blockages of ionic current with specificity. However, to locate the damaged sites on a DNA chain and recognize them, we need to break through the limitation of low spatial resolution of traditional nanopores, and then extract the characteristic ionic current signals of different kinds of modifications. Graphene nanopores own a single-atom thickness, promising the single-base spatial resolution. By means of simulations and calculations, in this proposal, we focus on the assessment of graphene nanopores in the locating and recognition of damaged sites on a DNA chain at atomic and molecular level. Firstly, we expect to understand the molecular mechanism dominating the ionic current blockage-- particularly the intermolecular interactions within a graphene nanopore and free energy changes of ions translocation. And then, we will discuss the sensitivity of blocked ionic current towards the inherent structural differences of different kinds of damaged sites on DNA. Finally, the induced ionic current will be predicted during the translocation of damaged DNA in graphene nanopores, and a deep analysis of the characteristic ionic current for different kinds of DNA-damages will be carried out. Based on these investigations, we expect to supply a theoretical foundation for the improvement of the resolution of nanopore experiments further.

英文关键词： microchip electrophoresis;nanopore;DNA damage;single-molecule detection;molecular simulation