Bacterial Outer Membranes and Interactions with Proteins

革兰氏阴性菌的细胞质被一层由两层组成的膜包围：内膜（或外质体）和外膜（OM）。OM将周质与外部环境分离，并作为选择性屏障，阻止抗生素和胆汁盐等有毒分子进入细菌。这种选择性屏障对细菌在多样化和恶劣环境中的生存至关重要。该项目旨在深入了解细菌OMs的行为和对各种细菌的作用，膜蛋白在OM中的行为和与OM的相互作用，以及溶质分子，特别是抗生素如何通过OMs进入。这将完成使用最先进的分子建模和模拟。该项目还将形成一个OM的分子建模和模拟的一般方法的基础，该方法将通过CHARMM-GUI网站（www.charmm-gui.org）免费提供，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跨学科的计算生物物理学训练。特别是，该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。革兰氏阴性菌细胞质周围的细胞包膜由内膜、周质和外膜（OM）组成。OM的独特之处在于具有-桶膜蛋白和高度不对称的脂质双分子层，其内小叶含有磷脂，外小叶含有脂多糖（LPS）。本项目旨在通过建立可靠的全原子建模和模拟革兰氏阴性菌各种复杂OMs和各种OMs中膜蛋白的计算方法，对各种细菌OMs的结构和动力学、蛋白质与OMs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LPS/OM分子建模和模拟的通用方法奠定基础。该项目还寻求通过为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-GUI中的LPS Modeler和Outer Membrane Builder），促进对LPS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.