Amino Acid and Peptide Asssembly: Mechanisms and Structures

在这个由化学部化学结构、动态和机制B项目资助的项目中，加州大学圣巴巴拉分校的Michael T. Bowers教授正在研究肽组装的机制。由于淀粉样蛋白的形成，肽和蛋白质的组合可以导致许多毁灭性的疾病，如阿尔茨海默病。这是一个活跃的研究领域，因为它具有根本性的重要性，对健康也有潜在的影响。通过对模型氨基酸和多肽的研究，可以了解控制较大肽和蛋白质组装的因素，有助于开发新的治疗剂。该项目非常适合对各级科学家的教育，包括那些在科学领域代表性不足的科学家。向文图拉和圣巴巴拉地区的高中生开展外展活动也是该资助项目的一部分。该基金还资助了一个免费网站，该网站可以准确快速地计算模型结构的横截面。具体来说，这笔拨款主要集中在氨基酸和小肽的组装上。在这些研究中，离子迁移率质谱法（IMS-MS）是主要的研究工具。在与柏林弗里茨哈伯研究所的Gert von Helden小组的合作中，IMS-MS与弗里茨哈伯自由电子激光相结合，对氨基酸和小肽的低聚物的大小和形状进行光谱分析。总体目标是了解淀粉样蛋白级联的分子机制，淀粉样蛋白级联在与许多破坏性疾病相关的系统中经常被观察到。淀粉样蛋白假说认为，肽本身折叠并各向同性组装，直到达到系统依赖的大小，它们重新排列成β薄片，并迅速添加单体形成原纤维。该小组，在过去的NSF支持期间，观察到特定肽系统的这一过程。目前的项目旨在了解这些观察结果，并开发一种算法，该算法可以准确预测仅知道初级结构的肽或蛋白质形成淀粉样蛋白的倾向。

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Michael T. Bowers at the University of California at Santa Barbara are investigating the mechanism of peptide assembly. Peptide and protein assemblies can contribute to many devastating diseases such as Alzheimer's disease because of amyloid formation. This is an active area of research both for its fundamental importance and its potential impacts on health. Through the studies on model amino acids and peptides, factors that control larger peptide and protein assembly can be learned, which can help the development of new therapeutic agents. The project is well suited for the education of scientists at all levels, including those underrepresented in science. Outreach activities to high school students in the Ventura and Santa Barbara areas are also part of the funded project. A free website that allows the accurate and rapid calculation of cross sections of model structures is also supported by this grant. Specifically, this grant is focused on the assembly of amino acids and small peptides. In these studies, Ion Mobility based Mass Spectrometry (IMS-MS) is used as the main tool. In collaboration with the group of Gert von Helden at the Fritz Haber Institute in Berlin, IMS-MS is coupled with the Fritz Haber free electron laser to do spectroscopy on size and shape selected oligomers of both amino acids and small peptides. The overarching goal is to understand the molecular mechanism of the amyloid cascade that is often observed for peptides and proteins in systems related to many devastating diseases. The amyloid hypothesis states that peptides natively fold and isotropically assemble until at a system dependent size they rearrange to beta sheet and rapidly add monomers to form fibrils. The group, in past NSF support periods, observed this process for specific peptide systems. The current project seeks to understand these observations and to develop an algorithm that can accurately predict the predilection of a peptide or protein to form amyloid knowing only the primary structure.