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

Liu, Shiyong; Pei, Jianfeng; Chen, Hao; Zhu, Xiaolei; Liu, Zhenming; Ma, Wenzhe; He, Fenglei; Lai, Luhua

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.