Modeling Membrane Dynamics and Permeation

项目摘要 这项建议考察了多肽通过生物运输的效率和选择性。 膜。多肽在生物学中被广泛应用于靶膜的渗透。他们 将材料输送到特定的单元格以及单元格。它们也被用作防御 抗其他生物的机制，如抗菌肽，或抗恶性细胞 (抗癌肽)。多肽功能的多样性和特异性使它们成为一种极好的 一项研究的目标，旨在将材料(药物)以惊人的精确度输送到选定的 牢房或牢房。一个跨学科的团队被组织起来研究多肽 与生物膜的相互作用包含了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 能够精确定位位置并测量各种不同的 穿过不同类型的膜的多肽，以及生物实验方面的专业知识 多肽渗透到活细胞的能力。跨学科团队是必要的，因为 由数千种不同类型的生物膜组成的极其复杂的生物膜 磷脂分子，以及许多其他成分，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。新颖的模拟和 开发了实验工具，使计算、预测和测量 膜和多肽的变化对通透性和功能的影响。选择性的变化 癌细胞和正常细胞的质膜的关系已经被阐明，并将进一步 研究旨在阐明分子机制的特异性并提供设计原则。这 预计该项目将阐明控制效率和 通过生物膜传递多肽的选择性，以及提供影响的途径 这些机制。

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.