摘要：本文运用同源建模，分子对接，分子动力学模拟和3D-QSAR等模拟方法对烟草天蛾的HMGR结构和课题组合成并测试抑制昆虫JH体内合成的偕二氟他汀类类似物进行初步研究，结果显示：可以通过人的HMGR晶体结构模建昆虫的HMGR三文结构，分子对接分析结果表明他汀类分子与昆虫HMGR的结合方式与人的HMGR结合方式不同，对比抑制HMGR的IC50值表示，初步说明HMGR可以作为农药新靶点的猜想是成立的，再通过分子动力学模拟结果中△Gbinding自由能大小进一步验证了这个猜想。所得的结论不仅对设计出高的酶活性，选择性和安全性statin药物提供指导，而且可以为开发一种新的绿色农药给予一定的理论指导。35405
毕业论文关键词：杀虫剂；三文定量构效关系；HMGR抑制剂；保幼激素
Abstract: The 3D-QSAR methods (CoMFA and CoMSIA) were used to study the relationship between the structures of gem-difluoro fluorine statin analogs which were synthesized by our group and their inhibition of insect JH biosynthesis in vitro. The manduca sexta HMGR structure and docking of their inhibitors were also studied with homology modeling, molecular docking and molecular dynamics simulations in this paper. Our results show: the human HMGR crystal structure modeling insect HMGR three-dimensional structure, molecular docking analysis showed different statin molecules and insect HMGR the binding mode and human HMGR binding mode, compared to inhibition with IC50 values HMGR said preliminary Description HMGR as a new target for pesticide guess is established through molecular dynamics simulations of the free energy △Gbinding size further validate this conjecture. The conclusion is not only to provide guidance on the design of a high activity, selectivity and safety of statins, but also for the development of a new green pesticide give particular theoretical guidance.
Keywords: Insecticide, 3D-QSAR, HMGR inhibitor, Juvenile Hormone
目录
1 绪论 1
1.1 研究背景和意义 1
1.1.1 绿色农药研发的必要性 1
1.1.2 靶标药物的简介 2
1.1.3 新型杀虫剂的简介 2
1.1.4 新型杀虫剂的作用方式 3
1.2 HMGR的简介 4
1.2.1 HMGR定义 4
1.2.1 以羟甲戊二酰辅酶A还原酶为靶标开展害虫防治的尝试 4
1.2.2 羟甲戊二酰辅酶A还原酶研究进展 6
1.3 计算机辅助药物设计的简介 7
1.3.1 CADD的定义 7
1.3.2 Sybyl软件的简介 7
1.3.3 定量构效关系 8
1.3.3.1 QSAR的发展 8
1.3.3.2 QSAQ中的结构参数 10
1.3.4 分子对接 11
1.4 研究内容 13
2 实验步骤 13
2.1 QSAR研究 13
2.1.1 分子构建和分子表单创建 13
2.1.2 分子叠合 17
2.1.3 CoMFA计算 17
2.1.4 PLS分析 17
2.1.5 模型活性预测 17
2.1.6 模型的等质图 17
2.2 分子对接 18
2.3 分子动力学模拟 18
3实验模型结果的分析与检验 19
3.1 3D-QSAR模型结果和分析 19
3.2 烟草天蛾和意峰的HMGR的同源建模结果分析 25
3.3 分子对接分析结果分析 28
3.4 分子动力学模拟结果分析 29
4 总结 31
5 致谢 32 HMGR为靶标的生态友好杀虫剂的设计:http://www.youerw.com/huaxue/lunwen_33328.html