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CAREER: Combining Research and Education via the Exploration of Peptide-Lipid Binding and Aggregation

职业：通过探索肽-脂质结合和聚集将研究和教育结合起来

基本信息

批准号：
1454948
负责人：
Silvina Matysiak
金额：
$ 65万
依托单位：
University of Maryland, College Park
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1454948&HistoricalAwards=false
关键词：
CAREER Combining Research Education via

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Silvina Matysiak from The University of Maryland, College Park to investigate how lipid composition affects peptide self-assembly pathways on a lipid membrane. The project involves the use of computational methods to establish how the chemistry of a lipid headgroup promotes peptide recruitment, misfolding and aggregation in the cases of several amyloidogenic peptides. These studies will provide fundamental information on vital conditions that promote or impede peptide self-assembly and that are responsible for the morphology of the resulting aggregates. The results of this project may be used to understand how protein misfolding in neurons may lead to neuronal dysfunction. As part of the project, several toolboxes will be created to teach parents and students at the high school and undergraduate levels, the importance of molecular interactions in the everyday world. In order to achieve this goal, real-time videos of living cells or animations will be combined with interactive hands-on modeling of proteins.There is a fundamental gap in understanding how proteins misfold and aggregate on cellular membranes. This project involves a computational investigation that aims at elucidating how membrane composition modulates amyloid peptide aggregation. A deeper understanding of the driving forces behind peptide aggregation on membranous surfaces would have impact on a number of disciplines ranging from biomaterials to biotechnology. The approaches involve an expansion of a previously developed coarse-grained model in the context of this project. The project aims to 1) study the role of peptide-lipid hydrogen bonds in peptide aggregation, 2) quantify the impact of electrostatic interactions in shaping aggregation pathways, 3) dissect the influence of multivalent ions in lipid domain formations and how this affects peptide energy landscapes and 4) characterize how changes in a membrane's physical properties can modify peptide aggregation behavior. The computational models developed in this award will be made freely available to the public.

有了这个奖项，化学部的生命过程化学计划正在资助马里兰州大学帕克分校的SilkenMatysiak博士研究脂质成分如何影响脂质膜上的肽自组装途径。该项目涉及使用计算方法来确定脂质头基的化学如何促进几种淀粉样蛋白生成肽的肽募集、错误折叠和聚集。这些研究将提供有关促进或阻碍肽自组装的重要条件的基本信息，这些条件对所得聚集体的形态负责。该项目的结果可用于了解神经元中的蛋白质错误折叠如何导致神经元功能障碍。作为该项目的一部分，将创建几个工具箱，以教导高中和本科阶段的家长和学生，分子相互作用在日常世界中的重要性。为了实现这一目标，活细胞或动画的实时视频将与蛋白质的交互式动手建模相结合。在理解蛋白质如何在细胞膜上错误折叠和聚集方面存在根本性的差距。这个项目涉及一个计算研究，旨在阐明膜成分如何调节淀粉样肽聚集。更深入地了解肽在膜表面聚集背后的驱动力将对从生物材料到生物技术的许多学科产生影响。这些方法涉及到在本项目的背景下，以前开发的粗粒度模型的扩展。该项目旨在1）研究肽-脂质氢键在肽聚集中的作用，2）量化静电相互作用在形成聚集途径中的影响，3）剖析多价离子在脂质结构域形成中的影响以及这如何影响肽能量景观，4）表征膜物理性质的变化如何改变肽聚集行为。在这个奖项中开发的计算模型将免费提供给公众。