基于碳纳米管的纳米孔系统的生物分子检测的模拟研究

项目名称： 基于碳纳米管的纳米孔系统的生物分子检测的模拟研究

项目编号： No.21473207

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 李敬源

作者单位： 浙江大学

项目金额： 85万元

中文摘要： 纳米孔生物检测研究，尤其是对寡核苷酸的检测是单分子生物研究领域的重要方向。基于碳纳米管的纳米孔系统具有孔径较小、检测灵敏度较高等优势。研究发现ClpXP蛋白酶水解底物过程中，底物蛋白发生受力去折叠并伴随多肽链转运过程。蛋白质这种特殊的去折叠-共转运行为及其受力几何关系，可在具有类似形状的碳纳米管系统中实现。本项目对碳纳米管系统中寡核苷酸的构象和运动以及泛素蛋白的去折叠-共转运行为进行模拟研究。讨论寡核苷酸构象与离子流量对核苷酸修饰基团的响应，探索降低寡核苷酸运动速度的方法(寡核苷酸运动速度过快是影响检测分辨率的重要原因）；研究蛋白质去折叠反应及构象变化过程，刻画去折叠过程关键步骤及对应的离子流量，研究碳纳米管内多肽链的转运速率及管径等因素的影响。上述研究将为进一步提高纳米孔检测的灵敏度和分辨率奠定基础，并探索纳米孔生物研究的新领域：蛋白质在一端受力情况下的去折叠-共转运行为。

中文关键词： 分子动力学；碳纳米管；纳米孔检测；寡核苷酸；蛋白质受力去折叠

英文摘要： The nanopore detection of single biological molecules, especially the oligonucleotide, is an important research field in the single molecule biology. Compared to protein nanopore and solid state nanopore systems, carbon nanotube (CNT) based nanopore has the advantages including small radius, regular structure, high detection sensitivity. Meanwhile, recent experimental studies found ClpXP protease can mechanically unfold protein substrate and translocate the denatured polypeptide through a pore within ClpXP. Such unique unfolding-co-translocation process can be realized in the CNT-based nanopore system which shares similar pore shape and pulling geometry. Here we propose to study the configuration and dynamic behavior of oligonucleotide together with the unfolding-co-translocation of ubiquitin in CNT-based nanopore system by molecular dynamics simulation. We are aim to study the impact of modification of single nucleotide on the configuration of oligonucleotide and the concurrent ion current, and probe the method to suppress the translocation speed of oligonucleotide: excessive translocation of molecules often results in limited nanopore detection resolution. We also plan to study the mechanical unfolding of ubiquitin and the accompanied conformational change, characterize the important steps of unfolding process and the corresponding ion current, and investigate the translocation of denatured polypeptide and the impact of CNT radius. These studies will be helpful for the further development of the sensitivity and resolution of nanopore detection and expand the nanopore studies to new biological process: the unfolding-co-translation of protein with one end mechanically loaded.

英文关键词： Molecular Dynamics;Carbon Nanotube;Nanopore Detection;Oligonucleotide;Protein Mechanical Unfolding