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).

人工纳米孔是新兴纳米版本（例如高通量DNA测序仪）的关键组成部分。它们在浓度和电压梯度下起作用，但是对这些条件下的选择性和纠正等通用问题的理解很少。模拟这些非平衡条件的计算方法仍然有限。在这里，我们将进行新型的稳态非平衡模拟（包括Langevin动力学，动态蒙特卡洛和局部平衡蒙特卡洛）Na+通道启发的纳米孔在与实验相同的条件下。这些条件包括在固定电压和固定电解质浓度的浴缸处的电极。这些边界条件为稳态运输提供了驱动力。首先，我们将重点关注开放状态的细菌NAVMS通道，为此提供实验性结构信息。野生型蛋白和突变体的模拟将通过全原子分子动力学计算完成。模拟的发现将根据我们的合作者C. Fahlke教授（德国的ForschungszentrumJülich）进行的实验进行测试。该建议扩展了美国和其他人以前开发的工具包，以构建通道和膜的粗粒（CG）模型。野生型和突变体NAVMS的CG模型在钾对钠的选择性方面最有前途的突变体（以及对二价对二价）的选择性和电压响应将用于提出人工纳米孔设计。电压响应包括通过在第三个电极上施加的电压对两个电极之间电流的整流和控制。纳米孔设计将通过CG模型的仿真测试，并将由我们的实验合作者Z. Siwy（美国加利福尼亚州的U. of US）构建和测试。