中文摘要：

甲状腺结合前清蛋白TTR是一种具有重要生理功能的蛋白质,它是约30种与淀粉样疾病相关的非同源蛋白中的一种。与TTR相关的淀粉样疾病主要有：家族淀粉化心肌疾病,家族淀粉化神经系统疾病,老年系统性淀粉样病变,以及中枢神经系统选择性淀粉化疾病等。这些疾病是由TTR四聚体解聚过程中错误折叠形成cross-β-sheet结构形态的淀粉样纤维所导致。本文介绍了TTR的生理功能及结构特征,并综述了到目前为止用分子动力学模拟、分子对接和定量构效关系等方法在研究TTR淀粉样机理及TTR和小分子相互作用过程中的计算化学研究成果,为基于TTR结构的TTR淀粉样抑制剂药物分子的设计和筛选提供有力参考。

英文摘要：

Transthyretin（ TTR） is a tetramer protein,and it is one of around 30 non-homologic amyloidogenic human proteins related to amyloid diseases. The diseases related to TTR amyloid include familial amyloid cardiomyopathy（ FAC）,familial amyloid polyneuropathy（ FAP）,senile systemic amyloidosis（ SSA）,and central nervous system-selective amyloidosis（ CNSA）. These diseases are proposed to be due to the formation of TTR amyloid and the construction of cross-β-sheet subunit via TTR misfolding. In this review,w e describe the physiological characteristics and structural features of TTR,and summarize computational studies on TTR using molecular dynamics simulation, molecular docking and quantitative structure-activity relationships. These computational chemical studies demonstrate possible mechanisms of TTR amyloid formation and the binding abilities of small molecules and TTR,w hich may provide insights to discover and screen new inhibitors preventing TTR from misfolding.