CAJ | 학술논문

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-CoA환원매(간칭HMGR)시강혈지약물설계적중요파표,억제해매적활성가이유효지강저혈장총담고순수평,종이강저리환심뇌혈관질병적궤솔.수연이경유수충타정류약물작위HMGR억제제응용우림상,단시타정류약물적안전성,특별시장기복용적안전성일직비수관주,소이설계신형안전적HMGR억제제잉연십분박절.논문근거hHMGR적정체결구,이용Dock、FlexX、Autodock 3개정서건립료hHMGR억제제적허의사선모형,모형적가고성통과중복정체결구、대비대접타분화화합물적활성지간적상관성등방법득이험증,최후,분석각충대접연건적특점,지출료hHMGR억제제허의사선,특별시목사중응당주의적문제,이기위신형HMGR억제제적설계제공지도.
Elevated concentration of plasma cholesterol Was a major risk factor for the development of coronary heart disease.3-hydrox-y-3-methyl-glutaryl-CoA reductase(HMGR),the natural target and the rate-limiting enzyme in the cholesterol biosynthetic pathway,Was an attractive target in the searching for drugs to reduce plasma cholesterol concentrations.In this paper,based on hHMGR proteincrystal structure,by using the three programs Dock,FlexX,and Autodock,virtual screening models for hHMGR inhibitors were con-structed.Thees models were proved to be reliable through crystal structure reproducing and comparison of docking scores with the com-pounds'COR/CSI activities.Comparason of different docking methods shows that stepwised docking and consensus scoring were essen-tial for a successful virtual screening.Discussion on virtual screening was given,which would be helpful for the discovery of newHMGR inhibitors.