MOLECULAR DYNAMIC SIMULATION OF THE INHIBITION OF AGGREGATION OF AMYLOID WITH B

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 阿尔茨海默病(AD)的病理特征是由Aβ多肽组成的细胞外淀粉样物沉积。目前，只有对症疗法可用于治疗阿尔茨海默病，而且这些疗法的实用时间有限。淀粉样变性疾病(包括阿尔茨海默病、其他神经退行性疾病和青光眼)代表了慢性A-β产生的影响，因此以A-β为靶点是一种可行的追求。β淀粉样蛋白聚集成低聚物、原纤维、纤维，最终形成斑块，这是阿尔茨海默氏病的神圣标志。各种小分子抗聚集抑制剂在文献中已有报道，但缺乏对它们与Aβ肽低聚物和纤维相互作用的详细描述。我们正在使用分子动力学软件包(安装在Stokes中的Amber9)对这些多肽的聚集抑制进行分子动力学模拟。我们的模拟将在原子水平上揭示我们的小有机分子与A-β寡聚体之间的相互作用，为设计具有治疗阿尔茨海默氏病、其他神经退行性疾病和青光眼潜力的聚集小分子抑制剂提供有用的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of A beta peptide. Presently, only symptomatic therapies are available for the treatment of AD and these therapies have a limited time frame of utility. Amyloid disorders (which include Alzheimer disease, other neurodegenerative disease and glaucoma) represent the effect of chronic A-beta production and therefore targeting A beta is a viable pursuit. The beta amyloids aggregate into oligomer, pro-fibril, fibril and eventually to plaques which is the hallow mark of Alzheimers disease. Various small molecules anti-aggregation inhibitors has been reported in the literature, yet, a detailed description of their interaction with the A beta peptides oligomers and fibrils is missing. We are implementing a molecular dynamic simulation of the inhibition of aggregation of these peptides using a molecular dynamic software package (Amber9 which is installed in stokes). Our simulation will shed light at atomic level on the interactions between our small organic molecules and the A-beta oligomers, providing useful insight for the design of small molecule inhibitors of aggregation with therapeutic potential for Alzheimers disease, other neurodegenerative disease and glaucoma.