INVESTIGATION OF MEMBRANE PROPERTIES TO UNDERSTAND PROTEIN FUNCTION MODULATION

研究膜特性以了解蛋白质功能调节

• 批准号: 8364254
• 负责人: TOBY WILLIAM ALLEN
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364254
• 关键词: Amino Acids; Biological; Biological Phenomena; Biomedical Research; Data; Drug Delivery Systems; Free Energy; Funding; Grant; High Performance Computing; Human Genome; Investigation; Ions; Lipid Bilayers; Lipids; Measures; Membrane; Membrane Proteins; Methods; Modeling; Molecular; National Center for Research Resources; Peptides; Permeability; Principal Investigator; Property; Proteins; Research; Research Infrastructure; Resources; Role; Sampling; Side; Source; United States National Institutes of Health; Viral; Work; analog; antimicrobial; cost; improved; membrane assembly; molecular dynamics; nanodevice; polypeptide; protein function; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A quantitative measure and molecular-level interpretation of protein-lipid interactions is essential to understand the partitioning, folding and function of membrane-proteins, which make up a third of the human genome and the majority of all drug targets. We aim to provide an understanding the physical rules that govern the assembly of membranes with their associated proteins using atomistic free energy molecular dynamics simulations. We will calculate free energy profiles of amino acid side chain analog molecules and ions to understand the energetics of permeation through a deformable lipid bilayer and to provide a renewed theoretical description of biological membranes. We will also continue to study the mechanisms of hydrophobic mismatch using polypeptides as model transmembrane segments and will begin simulations with polar sequences to understand new experimental data that challenges our hydrophobic matching concept. In addition, we will begin to explore the role of membrane composition on membrane deformability and permeability. We will also explore improved sampling methods for lipid bilayers. The results of this work have implications for a wide range of biological phenomena, including the activities of membrane proteins, antimicrobial and viral peptides, and bio-nanodevices.

这个子项目是利用这些资源的众多研究子项目之一