Modeling and Simulation of Bacterial Outer Membranes and Interactions with Proteins

细菌外膜及其与蛋白质相互作用的建模和模拟

基本信息

批准号：
1810695
负责人：
Wonpil Im
金额：
$ 61.67万
依托单位：
Lehigh University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1810695&HistoricalAwards=false
关键词：
Modeling Simulation Bacterial Outer Membranes

项目摘要

The outer membrane (OM) of Gram-negative bacteria is a unique and highly asymmetric lipid bilayer composed of phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. While LPS is the major component, the OM also contains the enterobacterial common antigens (ECAs) and capsular polysaccharides (CPS) whose occurrence is frequently overlooked. These unique cell surface glycolipids make the OM an effective, selective barrier against the permeation of toxic molecules such as antibiotics and bile salts into the bacteria, which causes significant threats to public health. This project seeks to acquire an understanding of structure and dynamics of the bacterial OMs and their interactions with the OM proteins using start-of-the-art molecular modeling and simulations. This project will also provide the basis for a general approach to OM molecular modeling and simulation. In particular, this project will raise the scientific literacy of the public through the educational outreach, publication of research results and workshop participation.This project aims to provide an in-depth and unprecedented understanding on structural and dynamics information of the OMs from various bacteria, interactions between proteins and OMs, and their influences on solute permeation by establishing reliable computational methods for all-atom modeling and simulation of various LPS/ECA/CPS-containing complex OMs of Gram-negative bacteria and membrane proteins in various OMs. It also seeks to foster synergistic scientific research and education on LPS/ECA/CPS molecules and bacterial OMs by providing reliable and general computational methods (through LPS/ECA/CPS Modelers and their incorporated into Membrane Builder in CHARMM-GUI, www.charmm-gui.org) to students and researchers in the simulation community and other disciplines.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

革兰氏阴性细菌的外膜（OM）是一种独特且高度不对称的脂质双层，由内部小叶中的磷脂和外部小叶中的脂多糖（LPS）组成。尽管LPS是主要成分，但OM还包含肠杆菌常见抗原（ECA）和囊囊多糖（CPS），其发生经常被忽略。这些独特的细胞表面糖脂使OM成为有效的，有选择性的屏障，以抵抗细菌的有毒分子（例如抗生素和胆汁盐）的渗透，这对公共卫生造成了重大威胁。该项目旨在通过使用启动的分子建模和模拟来了解细菌OMS的结构和动力学及其与OM蛋白的相互作用。该项目还将为OM分子建模和仿真的一般方法提供基础。特别是，该项目将通过教育宣传，研究结果的发布和研讨会参与来提高公众的科学素养。本项目旨在提供对OM的结构和动态信息的深入和前所未有的理解，从各种细菌的结构和动态信息中，蛋白质和OM之间的相互作用，蛋白质和OM之间的相互作用及其对溶质渗透性的影响以及它们的影响，以建立可靠的计算方法。革兰氏阴性细菌和膜蛋白中含有LPS/ECA/CPS的复合体。它还试图通过提供可靠和一般的计算方法（通过LPS/ECA/CPS建模者及其将其纳入Charmm-Gui的膜建造者，www.charmm-gui.org in Simers in Simers in Simers in Simers中，通过提供可靠和一般的计算方法来培养有关LPS/ECA/CPS分子和细菌OMS的协同科学研究和教育（通过LPS/ECA/CPS建模者及其将其纳入膜建造者）来培养协同的科学研究和教育。使命，并被认为是通过基金会的知识分子优点和更广泛影响的审查标准通过评估值得支持的。