CAREER: Deciphering Ionic Current Signatures of Polymer Transport through a Nanopore

职业：破译聚合物通过纳米孔传输的离子电流特征

• 批准号: 0955959
• 负责人: Aleksei Aksimentiev
• 金额: $ 42.5万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0955959&HistoricalAwards=false
• 关键词: CAREER; Deciphering; Ionic; Current; Signatures

TECHNICAL SUMMARYThis CAREER award supports computational and theoretical research and education on translocation of polymers through nanopores. Nanopores are ubiquitous in nature and engineering. Their functionality ranges from transport of solutes in and out of a living cell to chemical and biological separation and drug delivery. This research program investigates electric field-driven transport of a prototypical polymer DNA molecule through biological and synthetic nanopores and accompanying changes in co-passing ionic current used to characterize the transport by experiment. Nanopore translocation experiments enable testing of physical models of diverse nanoscale phenomena at the single-molecule level. They provide information about nanoscale electrostatics and hydrodynamics, solvation and entropic forces, selectro-osmotic effecs, atomic-scale friction, adhesion, and conformational dynamics of biopolymers. The fundamental difficulty in interpretation of the nanopore translocation experiments is that the microscopic processes of interest are characterized indirectly, by measuring their influence on the nanopore current. In order to more fully exploit the unprecedented sensitivity of nanopore probes, a quantitative physical model is required to relate the microscopic events in the nanopore to the measured ionic current. The PI aims to provide a comprehensive physical description of polymer transport through biological and synthetic nanopores through an innovative modeling method that combines all-atom molecular dynamics, Brownian dynamics, and multiscale simulations. This method will preserve the atomic-level information of the molecular dynamics method, while capitalizing on the computational efficiently of the Brownian dynamics and multiscale methods. The approach will exploit the thousandfold difference in the time scales of ion and polymer transport. The process of DNA transport through a nanopore will be characterized in statistical terms. The obtained ensemble of DNA conformations will be used to compute the corresponding ionic current blockades. The final step of the approach is to take into account the electro-kinetic effect that couples the ionic current to the polymer conformation. The main difference of this approach from the coarse-grained models that have been proposed to date is in preserving the all-atom information about the structure of the solute and nanopore and determining the ionic current blockade to the experimental accuracy. Combined with experiment, such predictive capability will greatly enhance utility of nanopores as tools to probe nanoscale systems and processes.This research program could have direct impact on nanopore applications in biosensing and nanotechnology, such as instrumentation for personal genomics, nanofluidic electronics, and single molecule manipulation. The educational activities will focus on developing a laboratory course and lecture demonstrations for an undergraduate biological physics course. Another major undertaking is transforming a graduate course "Physics of Nanomachines," into a textbook, which will describe the physics of nanoscale interactions that governs operation of miniature biological, synthetic, and hybrid machines. One very specific objective of the program is to recruit a minority student to carry out the research activities. The program will provide the research community with modeling methods and tools implemented by professional programmers in the popular Open Source programs, including a set of self-contained tutorials containing all necessary instructions and examples. NON-TECHNICAL SUMMARY:This CAREER award supports computational and theoretical research and education to simulate long chain-like molecules being pulled through tiny holes that have diameters the size of a large molecule. Of particular interest are long chain-like molecules produced by living organisms. These are often called biopolymers. For a brief moment, the molecule is confined to the small volume defined by the tiny molecule-sized hole, also known as a nanopore, and its properties can be examined section by section. It is thought that through the process of pulling the biopolymer through the tiny hole the shape and chemical makeup of the molecular string can be determined. The PI will focus on developing a comprehensive physical description of this process using novel computational modeling methods. The understanding that is gained could have direct impact on applications in biosensing and nanotechnology, such as sequencing DNA, future electronic devices, and single molecule manipulation. The educational activities will focus on developing a laboratory course and lecture demonstrations for an undergraduate biological physics course. Another major undertaking is transforming a graduate course "Physics of Nanomachines," into a textbook, which will describe the physics of interactions that governs operation of miniature biological, synthetic, and hybrid machines. One very specific objective of the program is to recruit a minority student to carry out the research activities. The program will provide the research community with modeling methods and tools implemented by professional programmers in the popular Open Source programs, including a set of self-contained tutorials containing all necessary instructions and examples.

该职业奖支持聚合物通过纳米孔易位的计算和理论研究和教育。纳米孔在自然界和工程中普遍存在。它们的功能范围从溶质进出活细胞的运输到化学和生物分离以及药物递送。该研究计划研究了电场驱动的原型聚合物DNA分子通过生物和合成纳米孔的运输，以及用于通过实验表征运输的共同通过离子电流的伴随变化。纳米孔移位实验使得能够在单分子水平上测试各种纳米级现象的物理模型。它们提供有关纳米静电和流体力学，溶剂化和熵力，选择渗透效应，原子尺度摩擦，粘附和生物聚合物的构象动力学的信息。解释纳米孔移位实验的根本困难在于，通过测量它们对纳米孔电流的影响，间接地表征感兴趣的微观过程。为了更充分地利用纳米孔探针前所未有的灵敏度，需要定量物理模型来将纳米孔中的微观事件与测量的离子电流相关联。PI旨在通过结合全原子分子动力学、布朗动力学和多尺度模拟的创新建模方法，提供聚合物通过生物和合成纳米孔传输的全面物理描述。该方法保留了分子动力学方法的原子级信息，同时利用了布朗动力学和多尺度方法的计算效率。该方法将利用离子和聚合物传输的时间尺度上的千倍差异。DNA通过纳米孔运输的过程将在统计方面进行表征。所获得的DNA构象的系综将被用来计算相应的离子电流封锁。该方法的最后一步是考虑将离子电流耦合到聚合物构象的电动效应。这种方法与迄今为止提出的粗粒度模型的主要区别在于保留了有关溶质和纳米孔结构的所有原子信息，并确定了实验精度的离子电流阻断。结合实验，这样的预测能力将大大提高实用性的纳米孔作为工具，探测纳米尺度的系统和processes.This研究计划可能有直接的影响，纳米孔在生物传感和纳米技术的应用，如个人基因组学，纳米流体电子学，和单分子操纵的仪器。教育活动将侧重于为本科生生物物理课程开发实验室课程和讲座演示。另一项主要任务是将研究生课程“纳米机器物理学”转化为教科书，该教科书将描述纳米级相互作用的物理学，该物理学控制微型生物、合成和混合机器的操作。该计划的一个非常具体的目标是招募一名少数民族学生开展研究活动。该计划将为研究社区提供由专业程序员在流行的开源程序中实现的建模方法和工具，包括一套包含所有必要说明和示例的自包含教程。 非技术总结：该职业奖支持计算和理论研究和教育，以模拟长链状分子通过直径与大分子大小相同的小孔被拉动。特别令人感兴趣的是由生物体产生的长链状分子。这些通常被称为生物聚合物。在很短的时间内，分子被限制在由微小分子大小的孔（也称为纳米孔）定义的小体积内，并且可以逐段检查其特性。人们认为，通过将生物聚合物拉过小孔的过程，可以确定分子串的形状和化学组成。PI将专注于开发一个全面的物理描述这一过程中使用新的计算建模方法。所获得的理解可能对生物传感和纳米技术的应用产生直接影响，例如DNA测序，未来的电子设备和单分子操作。教育活动将侧重于为本科生生物物理课程开发实验室课程和讲座演示。另一项主要任务是将研究生课程“纳米机器物理学”转化为教科书，其中将描述管理微型生物，合成和混合机器操作的相互作用物理学。该计划的一个非常具体的目标是招募一名少数民族学生开展研究活动。该计划将为研究社区提供由专业程序员在流行的开源程序中实现的建模方法和工具，包括一套包含所有必要说明和示例的自包含教程。