Zhang Zhen, Wu Gensheng, Wang Kaijia, Si Wei
Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, School of Mechanical Engineering, Southeast University, Nanjing 211100, China.
School of Mechanical and Electronic Engineering, Nanjing Forestry University, Nanjing 210037, China.
J Phys Chem B. 2025 Mar 6;129(9):2471-2481. doi: 10.1021/acs.jpcb.4c06968. Epub 2025 Feb 25.
Precise identification and quantification of amino acids are crucial for numerous biological applications. A significant challenge in the development of high-throughput, cost-effective nanopore protein sequencing technology is the rapid translocation of protein through the nanopore, which hinders accurate sequencing. In this study, we explore the potential of nanopore constructed from a novel two-dimensional (2D) material MoSiN in decelerating the velocity of protein translocation using molecular dynamics simulations. The translocation velocity of the peptide through the MoSiN nanopore can be reduced by nearly an order of magnitude compared to the MoS nanopore. Systematic analysis reveals that this reduction is due to stronger interaction between the peptide and MoSiN membrane surface, particularly for aromatic residues, as they contain aromatic rings composed of relatively nonpolar C-C and C-H bonds. By adjusting the proportion of aromatic residues in peptides, further control over peptide translocation velocity can be achieved. Additionally, the system validates the feasibility of using an appropriate nanopore diameter for protein sequencing. The theoretical investigations presented herein suggest a potential method for manipulating protein translocation kinetics, promising more effective and economical advancements in nanopore protein sequencing technology.
氨基酸的精确识别和定量对于众多生物学应用至关重要。在高通量、经济高效的纳米孔蛋白质测序技术发展中，一个重大挑战是蛋白质通过纳米孔的快速易位，这阻碍了准确测序。在本研究中，我们使用分子动力学模拟探索了由新型二维（2D）材料MoSiN构建的纳米孔在降低蛋白质易位速度方面的潜力。与MoS纳米孔相比，肽通过MoSiN纳米孔的易位速度可降低近一个数量级。系统分析表明，这种降低是由于肽与MoSiN膜表面之间更强的相互作用，特别是对于芳香族残基，因为它们含有由相对非极性的C-C和C-H键组成的芳香环。通过调整肽中芳香族残基的比例，可以进一步控制肽的易位速度。此外，该系统验证了使用合适的纳米孔直径进行蛋白质测序的可行性。本文提出的理论研究表明了一种操纵蛋白质易位动力学的潜在方法，有望在纳米孔蛋白质测序技术方面取得更有效和经济的进展。
