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

通过这一奖项，化学部生命过程化学项目资助马里兰大学园区分校的Silvina Matysiak博士研究脂类成分如何影响脂膜上的多肽自组装途径。该项目涉及使用计算方法来确定在几种淀粉样多肽的情况下，类脂头基的化学如何促进多肽的招募、错误折叠和聚集。这些研究将提供促进或阻碍多肽自组装的重要条件的基本信息，以及对所产生的聚集体的形态负责的关键条件。该项目的结果可能被用来理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，向高中和本科生的父母和学生传授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动手建模相结合。在理解蛋白质如何错误折叠和聚集在细胞膜上方面存在着根本的差距。该项目涉及一项旨在阐明膜成分如何调节淀粉样多肽聚集的计算研究。更深入地了解膜表面多肽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。这些方法涉及在该项目的背景下扩展先前开发的粗粒度模型。该项目旨在1)研究多肽-脂质氢键在多肽聚集中的作用，2)量化静电相互作用在形成聚集途径中的影响，3)剖析多价离子在脂域形成中的影响以及这种影响是如何影响多肽能量格局的，以及4)表征膜物理性质的变化如何改变多肽聚集行为。在本奖项中开发的计算模型将免费向公众提供。

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.