Pseudomonas aeruginosa Outer Membrane Protein Modeling

铜绿假单胞菌外膜蛋白模型

基本信息

批准号：
7189888
负责人：
T P STRAATSMA
金额：
$ 34.52万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7189888
关键词：
Address Antibiotics Behavior Binding Charge Computer Simulation Computer software Computing Methodologies Development Disruption Divalent Cations Electronics Electrostatics Elements Environment Escherichia Exhibits Free Energy Gentamicins Goals Gram-Negative Bacteria Human Infection Integral Membrane Protein Ion Channel Protein Ions Laboratories Lipid Bilayers Lipopolysaccharides Location Membrane Membrane Proteins Methods Microbe Modeling Molecular Molecular Models Oligosaccharides OmpA protein Permeability Phosphorylation Procedures Proteins Pseudomonas aeruginosa Research Personnel Resistance Role Salmonella typhimurium Shewanella Structure Suggestion Thermodynamics Vibrio cholerae Work aquatic organism base carboxylate computational chemistry design inorganic phosphate interest membrane model microbial model design models and simulation molecular dynamics molecular modeling pathogen porin programs simulation small molecule tool

项目摘要

DESCRIPTION (provided by applicant): This proposal outlines the development and application of new modeling and simulation capabilities for the study of the outer membrane proteins of Pseudomonas aeruginosa and Escherichia coil in realistic, atomicdetail models of the lipopolysaccharide (LPS) membrane. Simulations of lipid bilayers membranes have contributed significantly to our understanding of their energetics and dynamics, as well as the function and dynamics of embedded proteins. However, because of the complexity of LPS membranes, this is not the case for the outer membranes and outer membrane proteins of Gram-negative bacteria. The goal of this work is to develop the computational capabilities to construct realistic models for LPS membranes with embedded outer membrane proteins for use in molecular dynamics simulations. Our focus will be on the outer membrane of P. aeruginosa, one of the most important opportunistic human pathogens, in comparison with the outer membrane of E. coil to determine the role of elements that are specifically found in the LPS structure of the outer membrane of P. aeruginosa. However, the tools and procedures that will be developed as part of the proposed work will be applicable to the study of outer "membranes of any Gram-negative microbe. The goals of this proposal will be achieved through extension and implementation of new capabilities of NWChem, our massively parallel computational chemistry software suite for electronic structure calculations and classical molecular dynamics simulations.

描述（由申请人提供）：该提案概述了新的建模和模拟功能的开发和应用，用于在脂多糖（LPS）膜的真实原子细节模型中研究铜绿假单胞菌和大肠杆菌的外膜蛋白。脂质双层膜的模拟极大地促进了我们对其能量学和动力学以及嵌入蛋白质的功能和动力学的理解。然而，由于LPS膜的复杂性，革兰氏阴性菌的外膜和外膜蛋白并非如此。这项工作的目标是开发计算能力，构建嵌入外膜蛋白的 LPS 膜的真实模型，用于分子动力学模拟。我们的重点将放在铜绿假单胞菌（人类最重要的机会性病原体之一）的外膜上，与大肠杆菌的外膜进行比较，以确定外膜 LPS 结构中特异发现的元素的作用铜绿假单胞菌。然而，作为拟议工作的一部分开发的工具和程序将适用于任何革兰氏阴性微生物的外“膜”的研究。该提案的目标将通过扩展和实施 NWChem 的新功能来实现，NWChem 是我们用于电子结构计算和经典分子动力学模拟的大规模并行计算化学软件套件。