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ERA-Chemistry: Design and synthesis of biologically inspired ion-conducting nanopores

ERA Chemistry：受生物启发的离子传导纳米孔的设计和合成

基本信息

批准号：
252093367
负责人：
Professor Dr. Paolo Carloni
金额：
--
依托单位：
Forschungszentrum Jülich
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/252093367?language=en
关键词：
ERA Chemistry Design synthesis biologically

项目摘要

Artificial nanopores are crucial components for emerging nanodevices such as high-throughput DNA sequencers. They function under concentration and voltage gradients, but generic issues such as selectivity and rectification under these conditions are poorly understood. Computational means to simulate these non-equilibrium conditions are still limited. Here we will carry out novel steady-state non-equilibrium simulations (including diverse techniques such as Langevin Dynamics, Dynamic Monte Carlo, and Local Equilibrium Monte Carlo) of Na+ channel-inspired nanopores under the same conditions as experiment. These conditions include electrodes at fixed voltages and baths of fixed electrolyte concentrations. These boundary conditions provide the driving force for the steady state transport. First, we will focus on the bacterial NavMs channel in the open state, for which experimental structural information is available. Simulations of the wild-type protein and of mutants will be complemented by all-atom Molecular Dynamics calculations. The findings of the simulations will be tested against experiments performed by our collaborator Prof. C. Fahlke (Forschungszentrum Jülich, Germany). This proposal extends a toolkit previously developed by us and others to construct coarse-grained (CG) models of channels and membranes. A CG model of the wild-type and mutant NavMs channel will be designed and simulated.The most promising mutants in terms of selectivity of potassium against sodium (and also of monovalent against divalent) and voltage response will be used to propose artificial nanopore designs. Voltage response includes rectification and control of current between two electrodes by the voltage applied at a third electrode. Nanopores designs will be tested by simulations of CG models and will be constructed and tested by our experimental collaborator Z. Siwy (U. of California at Irvine, US).

人工纳米孔是高通量 DNA 测序仪等新兴纳米设备的关键组件。它们在浓度和电压梯度下发挥作用，但人们对这些条件下的选择性和整流等一般问题知之甚少。模拟这些非平衡条件的计算手段仍然有限。在这里，我们将在与实验相同的条件下对Na+通道启发的纳米孔进行新颖的稳态非平衡模拟（包括朗之万动力学、动态蒙特卡罗和局部平衡蒙特卡罗等多种技术）。这些条件包括固定电压的电极和固定电解质浓度的浴。这些边界条件为稳态传输提供了驱动力。首先，我们将重点关注处于开放状态的细菌 NavMs 通道，该通道可以获得实验结构信息。野生型蛋白质和突变体的模拟将得到全原子分子动力学计算的补充。模拟结果将根据我们的合作者 C. Fahlke 教授（德国于利希研究中心）进行的实验进行测试。该提案扩展了我们和其他人之前开发的工具包，用于构建通道和膜的粗粒度（CG）模型。将设计和模拟野生型和突变型 NavMs 通道的 CG 模型。在钾对钠选择性（以及单价对二价选择性）和电压响应方面最有前途的突变体将用于提出人工纳米孔设计。电压响应包括通过施加在第三电极上的电压对两个电极之间的电流进行整流和控制。纳米孔设计将通过 CG 模型模拟进行测试，并将由我们的实验合作者 Z. Siwy（美国加州大学欧文分校）构建和测试。