Bacterial Outer Membranes and Interactions with Proteins

革兰氏阴性细菌的细胞质由两层膜组成：内膜(或周质)和外膜(OM)。OM将周质与外部环境分开，起到选择性屏障的作用，防止抗生素和胆盐等有毒分子进入细菌。这种选择性屏障对细菌在不同和恶劣环境中的生存至关重要。该项目旨在从分子水平深入了解细菌膜如何作用于不同类型的细菌，膜蛋白如何在膜中表现并与膜相互作用，以及溶质分子，特别是抗生素，如何通过膜进入膜。这将使用最先进的分子建模和模拟来完成。该项目还将为有机质分子建模和模拟的一般方法奠定基础，该方法将通过CHARMM-图形用户界面网站(www.charmm-gui.org)免费获得，以便不同学科的研究人员可以研究其他重要的OM和相关蛋白质。研究生和本科生都将接受计算生物物理学跨学科学科的培训。特别是，这个项目将通过发表研究成果和参加研讨会来提高公众的科学素养。革兰氏阴性细菌细胞质周围的细胞膜由内膜、周质和外膜(OM)组成。OM的独特之处在于它具有β-桶状膜蛋白和高度不对称的脂双层，内叶含有磷脂，外叶含有脂多糖(LPS)。本项目旨在通过建立可靠的全原子模拟和模拟各种革兰氏阴性细菌膜蛋白和膜蛋白复合膜的计算方法，对各种细菌膜的结构和动力学、蛋白质与膜蛋白之间的相互作用及其对抗生素渗透的影响提供前所未有的深入了解。该研究将为脂多糖/有机化合物分子建模和模拟的一般方法奠定基础。该项目还寻求通过向模拟社区和其他学科的学生和研究人员提供可靠和通用的计算方法(通过CHARMM-图形用户界面中的脂多糖Modeler和外膜生成器)，促进关于脂多糖分子和细菌OMS的协同科学研究和教育。

The cytoplasm of gram-negative bacteria is surrounded by a membrane composed of two layers: the inner membrane (or periplast) and the outer membrane (OM). The OM separates the periplasm from the external environment and functions as a selective barrier that prevents the entry of toxic molecules such as antibiotics and bile salts into the bacteria. This selective barrier is crucial for survival of bacteria in diverse and hostile environments. This project seeks to acquire an in-depth and molecular-level understanding of how the bacterial OMs behave and work for various types of bacteria, how membrane proteins behave in the OM and interact with the OM, and how solute molecules, especially antibiotics, can enter through the OMs. This will be accomplished using start-of-the-art molecular modeling and simulations. This project will also form the basis for a general approach for molecular modeling and simulation of the OM that will be freely available through the CHARMM-GUI website (www.charmm-gui.org) so that researchers in various disciplines can investigate other important OMs and associated proteins. Both graduate and undergraduate students will be trained in the interdisciplinary discipline of computational biophysics. In particular, this project will raise the scientific literacy of the public through the publication of research results and workshop participation.The cell envelope surrounding a gram-negative bacteria's cytoplasm is composed of an inner membrane, the periplasm, and an outer membrane (OM). The OM is unique in terms of having beta-barrel membrane proteins and a highly asymmetric lipid bilayer containing phospholipids in its inner leaflet and lipopolysaccharide (LPS) in its outer leaflet. This project aims to provide an in-depth and unprecedented understanding of the structural and dynamics of the OMs from various bacteria, interactions between proteins and OMs, and their influences on antibiotic permeation by establishing reliable computational methods for all-atom modeling and simulation of various complex OMs of gram-negative bacteria and membrane proteins in various OMs. The research will found the basis for a general approach of LPS/OM molecular modeling and simulation. This project also seeks to foster synergistic scientific research and education on LPS molecules and bacterial OMs by providing reliable and general computational methods (through LPS Modeler and Outer Membrane Builder in CHARMM-GUI) to students and researchers in the simulation community and other disciplines.