Microscopic kinetics of DNA translocation through synthetic nanopores
Microscopic kinetics of DNA translocation through synthetic nanopores
复制标题
DOI：
10.1529/biophysj.104.042960
复制
发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Aksimentiev, A;Heng, JB;Schulten, K
我们以前已经证明，在纳米厚的金属氧化物半导体兼容膜上的纳米直径的孔可以用作检测DNA的分子传感器。使用这种类型的设备进行DNA测序的前景正在被热切地追寻。该传感器的关键属性是电场诱导(电压驱动)的DNA分子在电解液中通过纳米孔穿过膜的移位。为了补充正在进行的开发这种孔和测量信号以响应DNA存在的实验研究，我们对DNA通过纳米孔的移位进行了分子动力学模拟。一个典型的模拟系统包括一片氮化硅薄膜，将氯化钾的水溶液分成两个由纳米孔连接的隔室。外加电场诱导溶液中的小孔捕获DNA分子，并随后发生移位。分子动力学模拟表明，在典型的电场作用下，20碱基的双链DNA片段可以在几微秒内穿过2.2×2.6 nm(2)横截面的纳米孔。DNA碱基和孔表面之间的疏水相互作用可以减缓单链DNA的移位，并可能有利于双链DNA在孔内的解压。封闭孔口的DNA阻止了通过孔口的电解流；这些电流阻塞的程度与DNA通过孔口时观察到的阻塞程度相同。研究了用分子动力学模拟将阻断离子电流的水平与DNA序列联系起来的可行性。
We have previously demonstrated that a nanometer-diameter pore in a nanometer-thick metal-oxide-semiconductor-compatible membrane can be used as a molecular sensor for detecting DNA. The prospects for using this type of device for sequencing DNA are avidly being pursued. The key attribute of the sensor is the electric field-induced (voltage-driven) translocation of the DNA molecule in an electrolytic solution across the membrane through the nanopore. To complement ongoing experimental studies developing such pores and measuring signals in response to the presence of DNA, we conducted molecular dynamics simulations of DNA translocation through the nanopore. A typical simulated system included a patch of a silicon nitride membrane dividing water solution of potassium chloride into two compartments connected by the nanopore. External electrical fields induced capturing of the DNA molecules by the pore from the solution and subsequent translocation. Molecular dynamics simulations suggest that 20-basepair segments of double-stranded DNA can transit a nanopore of 2.2x2.6 nm(2) cross section in a few microseconds at typical electrical fields. Hydrophobic interactions between DNA bases and the pore surface can slow down translocation of single-stranded DNA and might favor unzipping of double-stranded DNA inside the pore. DNA occluding the pore mouth blocks the electrolytic current through the pore; these current blockades were found to have the same magnitude as the blockade observed when DNA transits the pore. The feasibility of using molecular dynamics simulations to relate the level of the blocked ionic current to the sequence of DNA was investigated.