细菌的多药耐药性问题使得抗感染治疗愈加的困难和复杂化。传统的抗生素已经无法满足当前的临床治疗需求，因此研发基于新靶点新机制的抗菌药物已迫在眉睫。本课题组已证实，长链抗菌肽BmK AGP-SYPU4，具有良好的抗菌活性，但并不破坏生物膜结构。据此，我们推测“长链抗菌肽BmK AGP-SYPU4杀菌机制主要通过作用于细胞膜上的钠离子通道，使其始终处于激活状态而导致细胞内钠离子的持续外流。”本课题首先构建该活性肽和细菌钠通道的空间结构，应用同源模建、分子对接和分子动力学等多尺度模拟方法，从原子和分子层面证明我们的假说，进一步应用分子生物学实验验证该活性肽的效应靶点及作用机制。本课题首次在原子、分子及细胞水平上探讨以细菌钠离子通道为靶点的抗菌肽作用机制，对抗菌肽的分子设计和开发新型抗菌药物具有非常重要的理论指导意义，而且为创制具有完全自主知识产权的多肽药物提供新型候选分子。

Multidrug resistance (MDR) problem of bacteria makes anti-infective therapy more difficult and complicated. Traditional antibiotics have been unable to meet the current clinical needs, so it is imminent to develop new antimicrobial drugs based on new targets and mechanisms. We have confirmed that the long-chain antibacterial peptide BmK AGP-SYPU4 has good antibacterial activity, but does not destroy the biomembrane structure. Accordingly, we conjecture that the long-chain antibacterial peptide BmK AGP-SYPU4 could sterilize the germ by activating the sodium channel on the cell membrane and making the sodium ion flowing out continuously. In this issue, we will build the spatial structure of the antibacterial peptide BmK AGP-SYPU4 and germ sodium ion channels. Multiscale simulation methods such as homology modeling, molecular docking and molecular dynamics will be used to prove our hypothesis, and then we could use biological experiments to verify the target and mechanism of the antimicrobial peptides. Our subject will explore the mechanism of the antibacterial peptide BmK AGP-SYPU4 based on the germ sodium channel for the first time in atomic, molecular and cellular levels. This issue will offer very important theoretical significance for antimicrobial peptides of molecular design and development of new antibacterial drugs, and provide new candidate molecules for creating completely independent intellectual polypeptide drugs.