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

合作研究：褶皱β-片层和波纹β-片层肽纳米原纤维的比较研究

• 批准号: 1904364
• 负责人: Cristiano Dias
• 金额: $ 28.25万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904364&HistoricalAwards=false
• 关键词: Collaborative; Research; Comparative; Studies; Pleated

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.

通过该奖项，化学系的大分子，超分子和纳米化学计划资助了来自罗切斯特大学的Bradley L. Nilsson博士，以及来自新泽西技术学院的Cristiano Dias博士，来自新泽西技术研究所的Cristiano Dias博士，研究了促进Beta-Sheet肽组装的结构和分子驱动力。 肽是在所有生物体中发现的自然存在的生物分子。 在细胞中，它们执行许多生物学功能，例如充当激素。 β表是与许多人类疾病相关的肽组件中发现的一种常见结构，其中最值得注意的是阿尔茨海默氏病。 在这项工作中，使用补充实验和计算技术研究了两个彼此镜像的肽的共组装。 这些努力可能会对决定自然和人工β表组装的分子尺度相互作用提供批判性见解。 这项研究可以简化并指导合理设计和合成下一代纳米材料与精确组织的肽的努力。与这项工作相关的外展活动包括基于查询的小型水凝胶，称为“凝胶或不凝胶：粘液科学：粘液科学”，这是在这两个机构进行的。 此外，这两个研究团队在夏季期间主持高中实习生六个星期，以提供指导并增加对科学研究和化学科学的兴趣。这项工作可能会提供重大的社会益处，因为它有可能洞悉涉及β-材料自组装的疾病机制，例如在阿尔茨海默氏病和一般的淀粉样蛋白中，这项研究的重点是对结构和分子的基本了解，并促进L-肽和D肽序列的Rippled beta beta beta nan nan nan nan nan nan nan。这使新肽序列的合理设计可以形成波纹的β-折叠纳米纤维系统。在第一个目标中，使用互补的实验和理论方法来表征打褶beta片和波纹β-β片纳米纤维的比较结构。 第二个目标利用了从L-和D肽序列的波纹β-片纳米纤维的计算指导评估和设计中的理论。获得的知识不仅适用于这些特定材料，还适用于理解β-片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重大的社会利益，因为它有可能洞悉涉及Beta表格自组装的疾病机制，例如在阿尔茨海默氏病和一般的淀粉样变性中。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子优点和广泛的影响来评估NSF的法定任务。

项目成果

Effects of Ions and Small Compounds on the Structure of Aβ 42 Monomers

离子和小化合物对 Aβ 42 单体结构的影响

• DOI: 10.1021/acs.jpcb.0c09617
• 发表时间: 2021
• 期刊: The Journal of Physical Chemistry B
• 作者: Mahmoudinobar, Farbod;Nilsson, Bradley L.;Dias, Cristiano L.
• 通讯作者: Dias, Cristiano L.

Binding Mechanisms of Amyloid-like Peptides to Lipid Bilayers and Effects of Divalent Cations

类淀粉样肽与脂质双层的结合机制及二价阳离子的影响

• DOI: 10.1021/acschemneuro.1c00140
• 发表时间: 2021
• 期刊: ACS Chemical Neuroscience
• 影响因子: 5
• 作者: Yang, Yanxing;Jalali, Sharareh;Nilsson, Bradley L.;Dias, Cristiano L.
• 通讯作者: Dias, Cristiano L.

Role of Cholesterol on Binding of Amyloid Fibrils to Lipid Bilayers

• DOI: 10.1021/acs.jpcb.0c00485
• 发表时间: 2020-04-16
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Dias, Cristiano L.;Jalali, Sharareh;Cruz, Luis
• 通讯作者: Cruz, Luis

Peptide–Membrane Binding: Effects of the Amino Acid Sequence

肽-膜结合：氨基酸序列的影响

• DOI: 10.1021/acs.jpcb.2c06404
• 发表时间: 2023
• 期刊: The Journal of Physical Chemistry B
• 作者: Yang, Yanxing;Dias, Cristiano L.
• 通讯作者: Dias, Cristiano L.

Using all-atom simulations in explicit solvent to study aggregation of amphipathic peptides into amyloid-like fibrils

• DOI: 10.1016/j.molliq.2021.118283
• 发表时间: 2022-02-01
• 期刊: JOURNAL OF MOLECULAR LIQUIDS
• 影响因子: 6
• 作者: Jalali, Sharareh;Yang, Yanxing;Dias, Cristiano
• 通讯作者: Dias, Cristiano