The resistance of pathogens to traditional antibiotics is currently a global issue of enormous concern. As the discovery and development of new antibiotics become increasingly challenging, synthetic antimicrobial lipopeptides (AMLPs) are now receiving renewed attention as a new class of antimicrobial agents. In contrast to traditional antibiotics, AMLPs act by physically disrupting the cell membrane (rather than targeting specific proteins), thus reducing the risk of inducing bacterial resistance. In this study, we use microsecond-timescale atomistic molecular dynamics simulations to quantify the interaction of a short AMLP (C16-KKK) with model bacterial lipid bilayers. In particular, we investigate how fundamental transmembrane properties change in relation to a range of lipopeptide concentrations. A number of structural, mechanical, and dynamical features are found to be significantly altered in a non-linear fashion. At 10 mol% concentration, lipopeptides have a condensing effect on bacterial bilayers, characterized by a decrease in the area per lipid and an increase in the bilayer order. Higher AMLP concentrations of 25 and 40 mol% destabilize the membrane by disrupting the bilayer core structure, inducing membrane thinning and water leakage. Important transmembrane properties such as the lateral pressure and dipole potential profiles are also affected. Potential implications on membrane function and associated proteins are discussed.

中文翻译：

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抗菌脂肽与细菌脂质双层的相互作用。

病原体对传统抗生素的耐药性是目前全球范围内备受关注的问题。随着新抗生素的发现和开发变得越来越具有挑战性，合成抗菌脂肽 (AMLP) 作为一类新型抗菌剂现在重新受到关注。与传统抗生素相比，AMLP 通过物理破坏细胞膜（而不是针对特定蛋白质）起作用，从而降低了诱导细菌耐药性的风险。在这项研究中，我们使用微秒级原子分子动力学模拟来量化短 AMLP (C16-KKK) 与模型细菌脂质双层的相互作用。特别是，我们研究了基本的跨膜特性如何随着脂肽浓度范围的变化而变化。一些结构、机械、发现动态特征以非线性方式显着改变。在 10 mol% 浓度下，脂肽对细菌双层具有凝聚作用，其特征是每个脂质的面积减少和双层顺序增加。25 和 40 mol% 的较高 AMLP 浓度会破坏双层核心结构，从而导致膜变薄和漏水，从而使膜不稳定。侧压和偶极电位分布等重要的跨膜特性也会受到影响。讨论了对膜功能和相关蛋白的潜在影响。其特征在于每个脂质的面积减少和双层顺序增加。25 和 40 mol% 的较高 AMLP 浓度会破坏双层核心结构，从而导致膜变薄和漏水，从而使膜不稳定。侧压和偶极电位分布等重要的跨膜特性也会受到影响。讨论了对膜功能和相关蛋白的潜在影响。其特征在于每个脂质的面积减少和双层顺序增加。25 和 40 mol% 的较高 AMLP 浓度会破坏双层核心结构，从而导致膜变薄和漏水，从而使膜不稳定。侧压和偶极电位分布等重要的跨膜特性也会受到影响。讨论了对膜功能和相关蛋白的潜在影响。