INVESTIGATION OF MEMBRANE PROPERTIES TO UNDERSTAND PROTEIN FUNCTION MODULATION

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 蛋白质-脂质相互作用的定量测量和分子水平的解释对于理解膜蛋白的分配、折叠和功能至关重要，膜蛋白占人类基因组的三分之一，也是所有药物靶点的大多数。我们的目标是提供一个理解的物理规则，管理其相关的蛋白质与原子自由能分子动力学模拟膜的组装。我们将计算氨基酸侧链类似物分子和离子的自由能分布，以了解通过可变形脂质双层渗透的能量学，并提供一个新的生物膜的理论描述。我们还将继续研究疏水性错配的机制，使用多肽作为模型跨膜片段，并将开始模拟极性序列，以了解新的实验数据，挑战我们的疏水性匹配的概念。此外，我们将开始探索膜组成对膜变形性和渗透性的作用。我们还将探索改进的脂质双层采样方法。这项工作的结果对广泛的生物现象有影响，包括膜蛋白、抗菌肽和病毒肽以及生物纳米器件的活性。

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.