基于三级结构比对和网络分析对抗乙肝病毒药物的筛选

Screening of HBV inhibitors based on the protein tertiary structure alignment and network analysis

目的运用蛋白区块结构码技术和药物靶点网络对抗乙肝病毒药物进行筛选。方法采用拉米夫定作用的靶点区结构扫描晶体结构一维码数据库以期发现和拉米夫定靶点结构相似的潜在靶标。基于Drugbank数据库建立乙肝病毒相关药物靶点网络，并针对靶点结构比对结果建立相应的乙肝病毒相关药物靶点子网络。对所预测的子网络中药物同药物靶点网络中的药物进行比较分析。结果预测结果显示，14个靶蛋白结构和拉米夫定作用靶点结构相似。所预测的子网络中的13种药物位于已知的药物靶点网络中。已上市药物中更昔洛韦和阿昔洛韦可能对乙肝病毒有较强抑制作用。结论本研究从结构生物学和药物靶点网络角度筛选新的乙肝病毒抑制剂，进而为临床新药的开发提供有益的线索。

Objective To screen the HBV inhibitors by use of protein tertiary structure alignment and network analysis. Methods Use of the target areas fragments of lamivudine to screen the crystal structure one-dimensional code database in order to discover the potential drug targets similar to the target areas of lamivudine. Construct HBV-retated drug-target networks and the sub-networks based on the drugbank database and the results of drug-target structures alignment. Make analysis of the drugs in the sub- networks. Result The result shows that, 14 structures of drug target proteins were similar to the target areas of lamivudine. 13 drugs in the sub-networks exist in the drug-target networks. The following two drugs gancielovir and Aciclovir may have strong inhibition to HBV. Conclusion Small-molecule screen identifies HBV inhibitors from a structure view and drug-target networks. It also provides useful clues for the development of new HBV inhibitors.