利用Markov模型研究Aβ突变体的构象转变过程  

Using Markov Model to Study ConformationalTransformation Process of A β Mutant

作　　者：姚星宇 刘璎锐 韩葳葳 万由衷 YAO Xingyu;LIU Yingrui;HAN Weiwei;WAN Youzhong(Bethune Third Clinical Hospital,Jilin University,Changchun 130033,China;School of Life Sciences,Jilin University,Changchun 130012,China)

机构地区：[1]吉林大学白求恩第三医院,长春130033 [2]吉林大学生命科学学院,长春130012

出　　处：《吉林大学学报（理学版）》2024年第1期174-180,共7页Journal of Jilin University:Science Edition

基　　金：吉林省科技厅计划发展项目(批准号:20230204044YY)。

摘　　要：为抑制淀粉样β多肽(Aβ)从无规卷曲或α-螺旋转变为β-折叠结构,研究野生型Aβ及其数组突变体的构象变化,结合Markov模型与分子动力学模拟,对野生型、A4型和D7N型Aβ的构象变化过程进行研究,明确3种Aβ构象的转变路径.实验结果表明,野生型Aβ出现一个区域的β-折叠,A4型Aβ构象几乎无变化,而D7N型Aβ出现两个区域的β-折叠,说明D7N型突变体具有促β-折叠特性,该结果为阿尔兹海默症的治疗方法探索提供理论依据.In order to suppress the transformation of amyloidβpolypeptide(Aβ)from random curling orα--helix toβ--folding structure,we studied the conformational changes of wild type Aβand its array mutants.Combining Markov model and molecular dynamics simulation,we studied the conformational change precess of the wild type,A4 type and D7N type Aβ,and identified the conformational transformation path of three Aβtypes.The experimental results show that one region ofβ--folding is found in the wild type Aβ,and the conformation of the A4 type Aβis almost unchanged,while two regions ofβ--folding are found in the D7N type Aβ,indicating that the D7N type mutant has the characteristic of promotingβ--folding.The results provide a theoretical baisis for exploring treatment methods for Alzheimer’s disease.

关 键 词：阿尔兹海默症 淀粉样β多肽 分子动力学模拟 MARKOV模型 

分 类 号：Q615[生物学—生物物理学]