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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 淀粉样变性与许多人类疾病有关，包括阿尔茨海默病、亨廷顿病和帕金森病以及影响大量人群的传染性海绵状脑病（朊病毒病）、II 型糖尿病。所有这些疾病共有的一个共同的病理过程是正常蛋白质转化为以β-折叠为主的纤维状蛋白质聚集体。需要增强对 β-折叠介导的聚集中分子事件的理解，以设计和实施有效的抑制和重折叠策略、提高折叠产量并设计治疗性抑制剂。我们建议通过全原子分子动力学模拟研究肽如何组装形成有序寡聚物，从而形成淀粉样原纤维。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。