Elucidating the impact of red blood cell membrane components on melittin-induced pore formation with molecular dynamics simulations

Understanding the membrane-disrupting mode of action of antimicrobial peptides (AMPs) in complex biological membranes is critical for the design of therapeutically viable AMPs that are both active against microbial pathogens and nontoxic to human cells. To assess human toxicity in AMP design studies, melittin (MEL) – a highly charged 26-amino acid AMP sourced from bee venom – is often used as the positive control in experimental human red blood cell (RBC) hemolysis assays. Molecular dynamics (MD) simulations have proved invaluable in elucidating the pore-formation mechanism of MEL in single-lipid zwitterionic membranes. However, modeling pore formation in lipid bilayers containing multiple lipid species, like RBC membranes, has been limited due to the challenges of using atomistic MD simulations to capture long-timescale membrane restructuring events that depend on lipid heterogeneity, leaflet asymmetry, and cholesterol content. To address these challenges and access larger time scales,..., , # Data from: Elucidating the impact of red blood cell membrane components on melittin-induced pore formation with molecular dynamics simulations Dataset DOI: [10.5061/dryad.ttdz08m92](10.5061/dryad.ttdz08m92) ## Description of the data and file structure ### Overview This work implements the nucleation collective variable ξ proposed by Hub et. al (10.1021/acs.jctc.7b00106) to expand on our recently developed coarse-grained to atomistic backmapping and umbrella sampling methodology (10.1021/acs.jpcb.4c03276) to rapidly resolve free energy profiles for melittin-lined pores in red blood cell (RBC) lipid membranes with molecular dynamics (MD) simulations. All simulations were run with [Gromacs 2021.5](https://manual.gromacs.org/2021.5/user-guide/getting-started.html) patched with PLUMED 2.8. ### Folder Structure The provided tarball (Supporting_Data.tar.gz) contains the following folders to aid with the reproducibility of the results of this work: * **analysis_output** --> Stores all...,解析抗菌肽（antimicrobial peptides, AMPs）在复杂生物膜中的膜破坏作用模式，对于研发兼具抗微生物病原体活性与人体细胞非毒性的治疗性可用抗菌肽至关重要。在抗菌肽的设计研究中，为评估人体毒性，蜂毒肽（melittin, MEL）——一种源自蜂毒的带高电荷的26肽抗菌肽——常被用作人体红细胞（red blood cell, RBC）溶血实验的阳性对照。分子动力学（molecular dynamics, MD）模拟已被证实可有效阐明蜂毒肽在单一脂类两性离子膜中的成孔机制。然而，由于原子级分子动力学模拟难以捕捉依赖于脂质异质性、膜叶不对称性与胆固醇含量的长时程膜重构事件，对包含多种脂质组分的脂质双层（如红细胞膜）的成孔建模研究仍受限于此。为解决上述挑战并拓展可访问的时间尺度…… 数据来源：《利用分子动力学模拟解析红细胞膜组分对蜂毒肽诱导成孔的影响》 数据集DOI：10.5061/dryad.ttdz08m92 ## 数据与文件结构说明 ### 概述 本研究采用Hub等人提出的成核集体变量ξ（参考文献：10.1021/acs.jctc.7b00106），并基于我们近期开发的粗粒化-原子化反向映射与伞形采样方法（参考文献：10.1021/acs.jpcb.4c03276），通过分子动力学模拟快速解析红细胞脂质膜中蜂毒肽衬底孔道的自由能分布。所有模拟均使用搭载PLUMED 2.8补丁的Gromacs 2021.5运行（https://manual.gromacs.org/2021.5/user-guide/getting-started.html）。 ### 文件夹结构 本研究提供的压缩包Supporting_Data.tar.gz包含以下文件夹，以保障研究结果的可重复性： * **analysis_output**：存储所有……