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Bacterial Outer Membranes and Interactions with Proteins

细菌外膜及其与蛋白质的相互作用

基本信息

批准号：
1727508
负责人：
Wonpil Im
金额：
$ 34.62万
依托单位：
Lehigh University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2019-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1727508&HistoricalAwards=false
关键词：
Bacterial Outer Membranes Interactions Proteins

项目摘要

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.

革兰氏阴性细菌的细胞质被由两层组成的膜包围：内膜（或周质体）和外膜（OM）。 OM 将周质与外部环境分开，并充当选择性屏障，防止抗生素和胆盐等有毒分子进入细菌。这种选择性屏障对于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 OM 的行为和对各种细菌的作用、膜蛋白在 OM 中的行为以及与 OM 的相互作用，以及溶质分子（尤其是抗生素）如何通过 OM 进入。这将通过最先进的分子建模和模拟来完成。该项目还将构成 OM 分子建模和模拟的通用方法的基础，该方法将通过 CHARMM-GUI 网站 (www.charmm-gui.org) 免费提供，以便各个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的培训。特别是，该项目将通过发表研究成果和参与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膜由内膜、周质和外膜（OM）组成。 OM 的独特之处在于具有 β 桶膜蛋白和高度不对称的脂质双层，其内层小叶含有磷脂，外层小叶含有脂多糖 (LPS)。该项目旨在通过建立可靠的计算方法来对各种复杂的革兰氏阴性细菌的 OM 和各种 OM 中的膜蛋白进行全原子建模和模拟，从而对各种细菌的 OM 的结构和动力学、蛋白质和 OM 之间的相互作用以及它们对抗生素渗透的影响提供深入和前所未有的了解。该研究将为 LPS/OM 分子建模和模拟的通用方法奠定基础。该项目还旨在通过向模拟界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 和外膜构建器），促进 LPS 分子和细菌 OM 的协同科学研究和教育。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Conformational States of the Cytoprotective Protein Bcl-xL

DOI：
10.1016/j.bpj.2020.08.014
发表时间：
2020-10-06
期刊：
BIOPHYSICAL JOURNAL
影响因子：
3.4
作者：
Ryzhov, Pavel;Tian, Ye;Marassi, Francesca M.
通讯作者：
Marassi, Francesca M.

Modeling and Simulation of Bacterial Outer Membranes with Lipopolysaccharides and Enterobacterial Common Antigen

DOI：
10.1021/acs.jpcb.0c03353
发表时间：
2020-07-16
期刊：
JOURNAL OF PHYSICAL CHEMISTRY B
影响因子：
3.3
作者：
Gao, Ya;Lee, Jumin;Im, Wonpil
通讯作者：
Im, Wonpil

Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival

Ail 和 LPS 在鼠疫耶尔森氏菌血清存活中的相互建设性作用

DOI：
10.1111/mmi.14530
发表时间：
2020
期刊：
Molecular Microbiology
影响因子：
3.6
作者：
Singh, Chandan;Lee, Hwayoung;Tian, Ye;Schesser Bartra, Sara;Hower, Suzanne;Fujimoto, Lynn M.;Yao, Yong;Ivanov, Sergey A.;Shaikhutdinova, Rima Z.;Anisimov, Andrey P.
通讯作者：
Anisimov, Andrey P.

Preferred conformations of lipooligosaccharides and oligosaccharides of Moraxella catarrhalis

DOI：
10.1093/glycob/cwz086
发表时间：
2020-02-01
期刊：
GLYCOBIOLOGY
影响因子：
4.3
作者：
Gao, Ya;Lee, Jumin;Im, Wonpil
通讯作者：
Im, Wonpil

Modeling of Specific Lipopolysaccharide Binding Sites on a Gram-Negative Porin

革兰氏阴性孔蛋白上特定脂多糖结合位点的建模

DOI：
10.1021/acs.jpcb.9b03669
发表时间：
2019
期刊：
The Journal of Physical Chemistry B
影响因子：
0
作者：
Kesireddy, Anusha;Pothula, Karunakar R.;Lee, Jumin;Patel, Dhilon S.;Pathania, Monisha;van den Berg, Bert;Im, Wonpil;Kleinekathöfer, Ulrich
通讯作者：
Kleinekathöfer, Ulrich