TOWARD UNDERSTANDING AMYLOIDOSIS: ALL-ATOM MOLECULAR DYNAMICS SIMUALTIONS OF AM

理解淀粉样变性：AM 的全原子分子动力学模拟

• 批准号: 7601390
• 负责人: YONG DUAN
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601390
• 关键词: Affect; Amyloid Fibrils; Amyloidosis; Biological Models; Computer Retrieval of Information on Scientific Projects Database; Disease; Event; Funding; Grant; Human; Institution; Lead; Link; Mediating; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Parkinson Disease; Pathologic Processes; Peptide Fragments; Peptides; Population; Prion Diseases; Proteins; Research; Research Personnel; Resources; Source; Staging; Therapeutic; United States National Institutes of Health; amyloid formation; beta pleated sheet; design; human disease; improved; inhibitor/antagonist; molecular dynamics; protein aggregate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloidosis has been linked to many human diseases, including Alzheimers, Huntingtons and Parkinsons and the transmissible spongiform encephalopathies (prion diseases), type II diabetes that affect large human population. A common pathological process shared by all these diseases is transformation of normal proteins to beta-sheet dominated fibrillar protein aggregates. An enhanced understanding of the molecular events in beta-sheet mediated aggregation is needed to design and implement effective inhibition and refolding strategies, improve folding yields, and design therapeutic inhibitors. We propose to study how peptides assemble to form ordered oligomers that lead to amyloid fibrils by all-atom molecular dynamics simulations. We will use small peptide fragments as the model systems to investigate the early stage formation of the amyloid protofibrils and their interactions with inhibitors.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 淀粉样变性与许多人类疾病有关，包括阿尔茨海默氏症，亨廷顿人和帕金森氏症以及可传播的海绵脑病（Prion疾病），影响大量人群的II型糖尿病。所有这些疾病共有的一个常见病理过程是将正常蛋白转化为β-谱主导的纤维蛋白聚集体。需要增强对Beta表中介导的聚合中分子事件的了解，以设计和实施有效的抑制和重新折叠策略，提高折叠产量并设计治疗性抑制剂。我们建议研究肽如何组装以形成有序的低聚物，从而通过全原子分子动力学模拟导致淀粉样蛋白纤维。我们将使用小肽片段作为模型系统来研究淀粉样原纤维的早期形成及其与抑制剂的相互作用。