基于各向异性网络模型分析A_(2A)腺苷受体变构过程中的关键残基

Analysis of key residues in A_(2A) adenosine receptor metamorphosis based on the anisotropic network model

A_(2A)腺苷受体(A_(2A) Adenosine receptor,A_(2A)AR)是A类G蛋白偶联受体的重要成员,在内源性激动剂腺苷介导的跨膜信号传导中发挥关键作用,参与许多重要的信号调节过程。基于各向异性网络模型,分析了A_(2A)AR非激活态、中间态以及激活态的快、慢运动模式残基的均方涨落,识别了A_(2A)AR变构过程中与结构稳定性及功能相关的关键残基。利用残基对间运动的相关性与相互作用,分析了A_(2A)AR变构过程中二级结构间的相关性和维持结构稳定的重要残基,研究结果为相关疾病与药物开发提供理论帮助。

A_(2A) adenosine receptor(A_(2A)AR),an important member of class A G-protein-coupled receptors,plays a critical role in transmembrane signaling mediated by endogenous agonist adenosine and is involved in many important signalregulatory processes.Using the anisotropic network model,we analyzed the mean-square fluctuations of residues in the inactive,intermediate,and active states of A_(2A)AR in both fast and slow-motion modes,and found the key residues that contribute to the structural stability and function of A_(2A)AR during its conformational changes.By examining the correlation and interaction of inter-residue pair motions,we investigated the correlation between the secondary structures and the important residues to maintain the structural stability in the A_(2A)AR allosteric process.The findings of this study provide theoretical guidance for the study of related diseases and drug development.