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HMG-CoA还原酶(简称HMGR)是降血脂药物设计的重要靶标,抑制该酶的活性可以有效地降低血浆总胆固醇水平,从而降低罹患心脑血管疾病的几率。虽然已经有数种他汀类药物作为HMGR抑制剂应用于临床,但是他汀类药物的安全性,特别是长期服用的安全性一直备受关注,所以设计新型安全的HMGR抑制剂仍然十分迫切。论文根据hHMGR的晶体结构,利用Dock、FlexX、Autodock 3个程序建立了hHMGR抑制剂的虚拟筛选模型,模型的可靠性通过重复晶体结构、对比对接打分和化合物的活性之间的相关性等方法得以验证,最后,分析各种对接软件的特点,指出了hHMGR抑制剂虚拟筛选,特别是目筛中应当注意的问题,以期为新型HMGR抑制剂的设计提供指导。
HMG-CoA reductase (referred to as HMGR) is an important target for lipid-lowering drug design. Inhibiting the activity of this enzyme can effectively reduce the level of total cholesterol in plasma and reduce the risk of cardiovascular and cerebrovascular diseases. Although several statins have been used clinically as HMGR inhibitors, the safety of statins, especially for long-term use, has drawn much attention, so it is still imperative to design new and safe HMGR inhibitors. According to the crystal structure of hHMGR, a virtual screening model of hHMGR inhibitor was established by using Dock, FlexX and Autodock programs. The reliability of the model was obtained by repeating the crystal structure, comparing the docking score and the correlation between the activity of the compound Finally, the characteristics of various docking softwares are analyzed. The virtual screening of hHMGR inhibitors, especially the problems that should be paid attention to, should be pointed out in order to provide guidance for the design of novel HMGR inhibitors.