Collaborative Research: Comparative Studies of Pleated beta-Sheet and Rippled beta-Sheet Peptide Nanofibrils

有了这个奖项，化学系的大分子，超分子和纳米化学项目资助了布拉德利L。来自罗切斯特大学的Nilsson和来自新泽西理工学院的Cristiano Dias博士研究了促进β折叠肽组装的结构和分子驱动力。 肽是在所有生物体中发现的天然存在的生物分子。 在细胞中，它们执行许多生物功能，例如充当激素。 β-折叠是在与许多人类疾病相关的肽组装体中发现的常见结构，其中最值得注意的是阿尔茨海默病。 在这项工作中，共同组装的两个肽是彼此的镜像研究使用互补的实验和计算技术。 这些努力可能会提供关键的洞察到分子尺度的相互作用，决定了组装的天然和人工β-片。 这项研究可以简化和指导合理设计和合成下一代具有精确组织的肽的纳米材料的努力。与这项工作有关的外联活动包括一个关于水凝胶的小型探究课程，名为“凝胶或不凝胶：粘液的科学”，在这两个机构进行。 此外，这两个研究小组在夏季接待了为期六周的高中实习生，以提供指导并提高对科学研究和化学科学的兴趣。这项工作可能会提供显着的社会效益，因为它有可能提供深入了解疾病的机制，涉及β-折叠自组装，如在阿尔茨海默氏症和淀粉样变性general.This研究的重点是获得基本的理解的结构和分子力驱动的L-和D-肽序列的共同组装成波纹β-折叠纳米原纤维。这使得能够合理设计可以形成波纹β-折叠纳米原纤维系统的新肽序列。在第一个目标中，互补的实验和理论方法被用来表征的比较结构的褶皱β-片和波纹β-片纳米原纤。 第二个目标利用理论在计算指导的评估和设计的波纹β-折叠纳米原纤维从L-和D-肽序列。所获得的知识可能不仅适用于这些特定的材料，而且还可以理解β-折叠结构在淀粉样蛋白自组装和蛋白质折叠中的作用。这项工作可能会提供显着的社会效益，因为它有可能提供深入了解疾病机制，涉及β-折叠自组装，如在阿尔茨海默氏症和淀粉样变性一般。这一奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

With this award, the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is funding Dr. Bradley L. Nilsson from University of Rochester and Dr. Cristiano Dias from New Jersey Institute of Technology to study the structure and molecular driving forces promoting the assembly of beta-sheet peptides. Peptides are naturally occurring biological molecules that are found in all living organisms. In cells, they perform many biological functions, for example acting as hormones. Beta-sheets are a common structure found in peptide assemblies associated with many human diseases, most notable of which is Alzheimer's disease. In this work, co-assembly of two peptides that are mirror images of one another is studied using complementary experimental and computational techniques. These efforts may provide critical insight into the molecular-scale interactions that dictate the assembly of both natural and artificial beta-sheets. The this research could simplify and guide efforts to rationally design and synthesize the next generation of nanomaterials with peptides that are precisely organized. Outreach activities associated with this work includes an inquiry based mini-course on hydrogels called "To Gel or Not To Gel: The Science of Slime" which is conducted at both institutions. Additionally, the two research teams host high school interns for six weeks during the summer to provide mentoring and increase interest in scientific research and chemical sciences in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.This research focuses on obtaining fundamental understanding of the structure and molecular forces driving the co-assembly of L- and D-peptides sequences into rippled beta-sheet nanofibrils. This enables the rational design of new peptide sequences that can form rippled beta-sheet nanofibril systems. In the first objective, complementary experimental and theoretical methods are used to characterize the comparative structures of pleated beta-sheet and rippled beta-sheet nanofibrils. The second objective exploits theory in the computationally-directed assessment and design of rippled beta-sheet nanofibrils from L- and D-peptide sequences. The knowledge obtained may be applicable not only to these specific materials, but also to understanding the role of beta-sheet structures in amyloid self-assembly and in protein folding in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.