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Nanopore Identification of Polyglutamine Length via Cross-Slit Sensing
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2024-11-18 , DOI: 10.1021/acs.jpclett.4c02681
Changxiong Huang, Huan Chen, Jun Luo, Ninggui Ma, Zhen Li, Xiao Cheng Zeng, Jun Fan

Nanopore sensing is now reshaping analytical proteomics with its simplicity, convenience, and high sensitivity. Determining the length of polyglutamine (polyQ) is crucial for the rapid screening of Huntington’s disease. In this computational study, we present a cross-nanoslit detection approach to determine the polyQ length, where the nanoslit is carved within a two-dimensional (2D) in-plane heterostructure of graphene (GRA) and hexagonal boron nitride (hBN). We designed a heterostructure with an hBN strip embedded in the graphene sheet. With such a design, polyQ peptides can spontaneously and linearly stretch out on the hBN stripe. By tuning the strength of an external in-plane electric field, molecular transportation of polyQ peptides along the hBN stripe can be effectively regulated. Subsequent cross-nanoslit motion can be applied to record time-dependent electric signals. The signal features are then utilized to train the machine learning classification models. The machine-learning-assisted recognition enables accurate determination of the protein’s length. This nanoslit-sensing method may offer theoretical guidance on 2D heterostructure design for the detection of polyQ peptide lengths and rapid screening of protein-related diseases.

中文翻译:


通过交叉狭缝传感鉴定聚谷氨酰胺长度的纳米孔



纳米孔传感现在正在以其简单、方便和高灵敏度重塑分析蛋白质组学。确定聚谷氨酰胺 (polyQ) 的长度对于亨廷顿舞蹈症的快速筛查至关重要。在这项计算研究中,我们提出了一种跨纳米狭缝检测方法来确定 polyQ 长度,其中纳米狭缝雕刻在石墨烯 (GRA) 和六方氮化硼 (hBN) 的二维 (2D) 平面内异质结构中。我们设计了一种异质结构,其中 hBN 条嵌入石墨烯片中。通过这样的设计,polyQ 肽可以在 hBN 条带上自发地线性伸展。通过调整外部面内电场的强度,可以有效地调节 polyQ 肽沿 hBN 条带的分子传输。随后的跨纳米狭缝运动可用于记录瞬态电信号。然后利用信号特征来训练机器学习分类模型。机器学习辅助识别能够准确确定蛋白质的长度。这种纳米狭缝传感方法可为 2D 异质结构设计提供理论指导,用于检测 polyQ 肽长度和快速筛查蛋白质相关疾病。
更新日期:2024-11-18
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