Coarse-grained modeling tools are employed to simulate the mechanics of DNA loading within a nanoscale confinement and predict semiflexible polymer conformations within the confinement, providing design recommendations for DNA-sequencing devices. A workflow is developed to quantify competing requirements of efficiency and accuracy and extract metrics that guide design optimization. The mean first-passage time for DNA loading is calculated as a function of the nanochannel geometry and the applied electric field. We analyze the interplay between the free energy of confinement and the electric potential energy in achieving high-throughput, base-pair detection. The single-read probability is investigated as informative metrics for sequencing accuracy and for sensing-strategy design. High cost, low throughput, and low accuracy have so far limited the adoption of nanochannel analysis and other long-read technologies. Our work directly addresses these limitations with a systematic approach that is scalable to long molecules and complex geometries.

中文翻译：

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通过纳米限制实现准确高效 DNA 测序的系统方法

粗粒度建模工具用于模拟纳米级限制内 DNA 加载的力学，并预测限制内的半柔性聚合物构象，为 DNA 测序设备提供设计建议。开发了一个工作流来量化效率和准确性的竞争要求，并提取指导设计优化的指标。DNA 加载的平均首次通过时间计算为纳米通道几何形状和施加电场的函数。我们分析了限制自由能和电势能在实现高通量碱基对检测中的相互作用。将单读概率作为测序准确性和传感策略设计的信息指标进行研究。成本高，吞吐量低，迄今为止，低准确度限制了纳米通道分析和其他长读长技术的采用。我们的工作通过一种可扩展到长分子和复杂几何形状的系统方法直接解决了这些限制。