Developing molecular models to capture the complex physicochemical architecture of the bacterial cell wall and to study the interaction with antibacterial molecules is an important aspect of assessing and developing novel antimicrobial molecules. We carried out molecular dynamics simulations using an atomistic model of peptidoglycan to represent the architecture for Gram-positive S. aureus. The model is developed to capture various structural features of the Staphylococcal cell wall, such as the peptide orientation, area per disaccharide, glycan length distribution, cross-linking, and pore size. A comparison of the cell wall density and electrostatic potentials is made with a previously developed cell wall model of Gram-negative bacteria, E. coli, and properties for both single and multilayered structures of the Staphylococcal cell wall are studied. We investigated the interactions of the antimicrobial peptide melittin with peptidoglycan structures. The depth of melittin binding to peptidoglycan is more pronounced in E. coli than in S. aureus, and consequently, melittin has greater contacts with glycan units of E. coli. Contacts of melittin with the amino acids of peptidoglycan are comparable across both the strains, and the D-Ala residues, which are sites for transpeptidation, show enhanced interactions with melittin. A low energetic barrier is observed for translocation of a naturally occurring antimicrobial thymol with the four-layered peptidoglycan model. The molecular model developed for Gram-positive peptidoglycan allows us to compare and contrast the cell wall penetrating properties with Gram-negative strains and assess for the first time binding and translocation of antimicrobial molecules for Gram-positive cell walls.

中文翻译：

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使用分子动力学模拟区分抗菌剂与革兰氏阴性和革兰氏阳性细菌细胞壁的相互作用

开发分子模型以捕获细菌细胞壁的复杂物理化学结构并研究与抗菌分子的相互作用是评估和开发新型抗菌分子的一个重要方面。我们使用肽聚糖的原子模型来表示革兰氏阳性金黄色葡萄球菌的结构，进行了分子动力学模拟。开发该模型是为了捕获葡萄球菌细胞壁的各种结构特征，例如肽方向、每个双糖的面积、聚糖长度分布、交联和孔径。将细胞壁密度和静电势与先前开发的革兰氏阴性细菌大肠杆菌细胞壁模型进行比较, 并研究了葡萄球菌细胞壁的单层和多层结构的特性。我们研究了抗菌肽蜂毒肽与肽聚糖结构的相互作用。蜂毒素与肽聚糖结合的深度在大肠杆菌中比在金黄色葡萄球菌中更明显，因此，蜂毒素与大肠杆菌的聚糖单元有更多接触. 蜂毒肽与肽聚糖氨基酸的接触在两种菌株中是相当的，并且作为转肽位点的 D-Ala 残基显示出与蜂毒肽的增强相互作用。使用四层肽聚糖模型观察到天然存在的抗菌百里酚易位的低能量屏障。为革兰氏阳性肽聚糖开发的分子模型使我们能够比较和对比细胞壁穿透特性与革兰氏阴性菌株，并首次评估抗菌分子对革兰氏阳性细胞壁的结合和易位。