SARS冠状病毒主要蛋白酶结构模建及活性部位运动性分析

Modeling of the SARS coronavirus main proteinase and conformational flexibility of the active site

SARS冠状病毒 3CL蛋白酶是病毒复制过程中的关键酶 ,有可能成为针对抗SARS药物研制的重要靶标。利用同源模建的方法建立了SARS冠状病毒 3CL蛋白酶的结构模型 ,对于二聚体中蛋白质分子间相互作用分析表明该蛋白在溶液中有可能形成二聚体。利用分子动力学与多正则系综采样相结合的方法对于SARS冠状病毒 3CL蛋白酶活性部位的两个环区进行了构象模拟 ,找到了两种代表性构象 ,预示着SARS冠状病毒

SARS coronavirus 3CL proteinase is the key enzyme for virus replication which may serve as the target for drug discovery against SARS. A 3D structure model has been built for SARS coronavirus 3CL proteinase by comparative protein modeling. A homodimer model of the proteinase was also built. Analysis of the dimeric interface suggests the 3CL proteinase may have dimer form in solution. The conformational flexibility of the active site has been simulated by molecular dynamics combined with multi canonical sampling. The active site loops have two typical conformations which may be related to the conformational movement associated with the enzymatic reaction.