NER: Molecular Dynamics Study of the Transverse Current During the Translocation of DNA Through a Fabricated Nanopore

0103140 Cui收到了对NSE，NSF-0019的响应。 探索一种新的快速DNA测序方法。将进行分子动力学模拟，以建立潜在的可行性，提出的方法，用于解决单个碱基的单链DNA在水电解质介质中被驱动通过人工制造的纳米横截面的通道由轴向电场。当完全伸长的DNA链上的各个碱基在电极之间被驱动时，电流变化的幅度和持续时间将在横向于通道轴定位的一对偏置电极之间确定。在这种计算中要探索的关键可行性问题是给定碱基的当前签名的再现性，一个碱基的签名与其他碱基的签名的可重复性，以及签名与随机波动相比的幅度。如果计算证明了这种方法的可行性，那么将有强烈的动机在实验和计算上进一步研究它，因为它提供了加速从ca. 0.3使用基于桑格方法的当前技术，可以将每秒的碱基数提高到每秒数百万到数十亿个碱基。这种快速测序可以使得能够在适合于个体诊断和基于基因组的治疗的时间尺度和成本内对个体基因组进行测序。今天存在的技术原则上允许制造钙的通道。2nm横截面，嵌入电极的尺寸与单个基底的尺寸相当。预计在今后几年内将实验性地实现这种系统。已经，在电驱动流过天然膜中的纳米级蛋白质孔期间进行DNA和RNA检测的实验引起了极大的兴趣，但这些系统远远达不到为研究提出的制造通道的承诺，并且还有许多其他缺点。在所提出的探索性模拟的成功是肯定的刺激和指导努力实现实验，并将提供优化和理解这些未来的实验的工具。

0103140CuiThis proposal was received in response to NSE, NSF-0019. A promising new method for rapid DNA sequencing will be explored. Molecular dynamics simulations will be performed to establish the potential feasibility of a proposed method for resolving individual bases of single-strand DNA in aqueous electrolyte medium being driven through an artificially fabricated channel of nanometer cross section by an axial electric field. The magnitude and duration of electrical current variations will be determined between a pair of biased electrodes positioned transverse to the channel axis, as individual bases on the fully-elongated DNA strand are driven between the electrodes. The crucial feasibility issues to be explored in this calculation are the reproducibility of the current signature of a given base, the distinguishability of one base's signature from others', and the magnitude of the signature compared with random fluctuations. If calculations demonstrate the feasibility of this approach, there will be strong incentive to study it further both experimentally and computationally, for it offers the potential to speed up DNA sequencing from ca. 0.3 bases per second using current technology based on the Sanger method to perhaps millions to billions of bases per second. Such rapid sequencing could enable sequencing of an individual genome within time scale and cost appropriate for individual diagnostics and genome-based treatment. Techniques exist today that, in principle, allow fabrication of channels of ca. 2 nm cross section with embedded electrodes of dimensions comparable to those of a single base. Experimental realization of such systems is expected within the next few years. Already, experiments with DNA and RNA detection during electrically-driven flow through nanometer scale protein pores in natural membranes have excited great interest, but these systems fall far short of the promise of the fabricated channels proposed for study and have many other disadvantages, as well. Success in the proposed exploratory simulations is certain to stimulate and guide efforts toward experimental realization and will provide the tools for optimizing and understanding these future experiments.