A Glycam-Based Force Field for Simulations of Lipopolysaccharide Membranes: Parametrization and Validation

作     者：Kirschner, Karl N. Lins, Roberto D. Maass, Astrid Soares, Thereza A. 

作者机构：Fraunhofer Inst Algorithms & Sci Comp SCAI Dept Bioinformat D-53754 Schloss Birlinghoven Sankt Augustin Germany Fraunhofer Inst Algorithms & Sci Comp SCAI Dept Simulat Engn D-53754 Schloss Birlinghoven Sankt Augustin Germany Univ Fed Pernambuco Dept Fundamental Chem BR-50740560 Recife PE Brazil 

出 版 物：《JOURNAL OF CHEMICAL THEORY AND COMPUTATION》 (化学理论与计算杂志)

年 卷 期：2012年第8卷第11期

页      面：4719-4731页

核心收录：

学科分类：07[理学] 0703[理学-化学] 0702[理学-物理学] 

基　　金：Brazilian National Council for Research and Development (CNPq) State of Pernambuco Research Foundation (FACEPE) INCT-INAMI nBioNet Nanobiotec-BR/CAPES Swedish Foundation for International Cooperation in Research and Higher Education (STINT) 

主　　题：Vesicles Lipids Molecules Membranes Molecular mechanics 

摘      要：Lipopolysaccharides (LPS) comprise the outermost layer of the Gram-negative bacteria cell envelope. Packed onto a lipid layer, the outer membrane displays remarkable physical-chemical differences compared to cell membranes. The carbohydrate-rich region confers a membrane asymmetry that underlies many biological processes such as endotoxicity, antibiotic resistance, and cell adhesion. Furthermore, unlike membrane proteins from other sources, integral outer-membrane proteins do not consist of transmembrane alpha helices;instead they consist of antiparallel beta-barrels, which highlights the importance of the LPS membrane as a medium. In this work, we present an extension of the GLYCAM06 farce field that has been specifically developed for LPS membranes using our Wolf(2)Pack program. This new set of parameters for lipopolysaccharide molecules expands the GLYCAM06 repertoire of monosaccharides to include phosphorylated N- and O-acetylglucosamine, 3-deoxy-D-manno-oct-2-ulosonic acid, L-glycero-D-manno-heptose and its O-carbamoylated Variant, and N-alanine-D-galactoamine. A total of 1 mu s of molecular dynamics simulations of the rough LPS membrane of Pseudomonas aeruginosa PA01 is used to showcase the added parameter set The equilibration of the LPS membrane is shown to be significantly slower compared to phospholipid membranes, on the order of 500 ns. It is further shown that Water molecules penetrate the hydrocarbon region up, to the terminal methyl groups, much deeper than commonly observed for. phospholipid bilayers, and in agreement. With neutron diffraction measurements. A comparison, Of simulated structural, dynamical, and electrostatic properties against corresponding experimentally available data shows that the present parameter set reproduces Well the overall structure and the permeability of LPS membranes in the liquid-crystalline phase.