Modeling Membrane Dynamics and Permeation

膜动力学和渗透建模

• 批准号: 10261358
• 负责人: ALFREDO CARDENAS
• 金额: $ 33.47万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261358
• 关键词: Adsorption; Algorithms; Amino Acids; Biological; Biology; Cell Compartmentation; Cell Culture Techniques; Cell membrane; Cells; Charge; Chemicals; Cholesterol; Circular Dichroism; Computer Analysis; Computer Simulation; Computing Methodologies; Defense Mechanisms; Environment; Event; Fluorescence; Free Energy; Grant; Heterogeneity; Hour; Human; Image; Integral Membrane Protein; Investigation; Kinetics; Label; Lead; Length; Light; Lipids; Location; Malignant - descriptor; Malignant Neoplasms; Measures; Membrane; Molecular; Normal Cell; Organelles; Organism; Outcome; Pathway interactions; Patients; Penetration; Peptide Transport; Peptides; Permeability; Pharmaceutical Preparations; Phospholipids; Physical Chemistry; Physics; Proteins; Pump; Reaction; Resolution; Sampling; Shapes; Specificity; Spectrum Analysis; System; Techniques; Time; Tryptophan; Variant; anti-cancer; antimicrobial peptide; base; biological systems; cancer cell; design; experience; experimental study; flexibility; improved; infrared spectroscopy; membrane model; millisecond; molecular dynamics; novel; screening panel; simulation; targeted agent; tool; trafficking

Project Summary This proposal examines the efficiency and selectivity of peptide transport through biological membranes. Peptides are widely used in biology to permeate through target membranes. They transport material to specific cells as well as cell compartments. They are also used as defense mechanisms against other organisms such as antimicrobial peptides, or against malignant cells (anticancer peptides). The diversity and specificity of peptide functions make them an excellent target for a study that aims to deliver material (drugs) with razor sharp accuracy into a selected cell or a cell compartment. An interdisciplinary team was assembled to study peptide interactions with biological membranes that encompass expertise in molecular dynamics simulations of biological molecules, expertise in physical chemistry experiments on biological systems that are able to pinpoint the location and measure the dynamics of a diverse set of peptides passing through different types of membranes, and expertise in biological experiments of peptide permeation into living cells. The interdisciplinary team is needed because of the tremendous complexity of biological membranes that are made of thousands types of different phospholipid molecules, and many other components such as cholesterol molecules and trans- membrane proteins. This complexity is necessary for membrane function. Novel simulation and experimental tools are developed that will make it possible to compute, predict and measure the impact of membrane and peptide variation on permeability and function. Variations in selectivity of the plasma membranes of cancer and normal cells were already illustrated and will be further investigated to elucidate specificity of molecular mechanisms and offer design principles. This project is expected to shed light on the detailed mechanisms that control the efficiency and selectivity of peptide transport through biological membranes, as well as offer avenues to impact these mechanisms.

项目摘要 该提案研究了肽通过生物转运的效率和选择性， 膜。肽在生物学中广泛用于渗透穿过靶膜。他们 将物质运输到特定的细胞以及细胞区室。它们也被用作防御 抗其他生物体如抗微生物肽或抗恶性细胞的机制 （抗癌肽）。肽功能的多样性和特异性使其成为一种极好的 一项研究的目标，旨在提供材料（药物）与剃刀锋利的准确性到一个选定的 细胞或细胞隔室。组建了一个跨学科的团队来研究肽 与生物膜的相互作用，包括分子动力学方面的专业知识 生物分子模拟，生物物理化学实验的专业知识 系统能够精确定位并测量各种各样的 肽通过不同类型的膜，并在生物实验的专业知识 肽渗透到活细胞中。需要跨学科团队，因为 生物膜的巨大复杂性是由数千种不同的 磷脂分子和许多其他成分，如胆固醇分子和反式- 膜蛋白这种复杂性是膜功能所必需的。新的模拟和 实验工具的开发，将有可能计算，预测和测量 膜和肽变化对渗透性和功能影响。选择性的变化 癌细胞和正常细胞的质膜已经被说明，并将进一步 研究阐明分子机制的特异性并提供设计原则。这 该项目预计将阐明控制效率的详细机制， 通过生物膜的肽运输的选择性，以及提供影响的途径 这些机制。