纳米孔
氨基酸
遗传密码
溶氧素
蛋白质工程
化学
分子动力学
生物分子
纳米技术
生物物理学
材料科学
生物化学
生物
酶
基因
计算化学
毒力
作者
Xueyuan Wu,Meng‐Yin Li,Shaojun Yang,Jie Jiang,Yi‐Lun Ying,Peng R. Chen,Yi‐Tao Long
标识
DOI:10.1002/anie.202300582
摘要
Abstract Conventional protein engineering methods for modifying protein nanopores are typically limited to 20 natural amino acids, which restrict the diversity of the nanopores in structure and function. To enrich the chemical environment inside the nanopore, we employed the genetic code expansion (GCE) technique to site‐specifically incorporate the unnatural amino acid (UAA) into the sensing region of aerolysin nanopores. This approach leveraged the efficient pyrrolysine‐based aminoacyl‐tRNA synthetase‐tRNA pair for a high yield of pore‐forming protein. Both molecular dynamics (MD) simulations and single‐molecule sensing experiments demonstrated that the conformation of UAA residues provided a favorable geometric orientation for the interactions of target molecules and the pore. This rationally designed chemical environment enabled the direct discrimination of multiple peptides containing hydrophobic amino acids. Our work provides a new framework for endowing nanopores with unique sensing properties that are difficult to achieve using classical protein engineering approaches.
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