摘要:癌症在现代人类生活中，常常威胁着人类的生命，影响着人类的健康以及生活质量，危及到人类的死亡。所以，积极研发新型抗肿瘤药物是抵抗癌症的方法之一。CombretastatinA-4是从南非灌木中提取出的活性组分，具有高效的抗肿瘤活性。本论文通过研究CombretastatinA-4的类似物来研究对乳腺癌MCF-7的生长抑制作用。本文通过计算机辅助药物设计软件SYBYL-X 2.0，根据收集到的数据建立合理的3D-QSAR模型，由分子对接、药效团虚拟筛选，设计出有效的新型抗肿瘤CombretastatinA-4类似物来抑制人乳腺癌MCF-7细胞毒性。用三文定量构效关系（3D-QSAR）方法建立了预测模型，采用抽一法(leave one out，LOO) 检验了预测模型的可信性，比较分子立场分析模型交叉验证系数q2 =0.832，相关系数R2=0.993，标准偏差为0.133， F值为583.114。比较分子相似度分析模型的交叉验证系数q2 =0.660，相关系数R2=0.984，标准偏差为0.195，F值为298.843。并用测试集进一步验证预测模型的预测能力。研究结果表明建立的3D-QSAR模型在统计学上具有明确、良好的预测能力。同时进行了药效团识别和虚拟筛选。根据所建模型的CoMFA、CoMISA模型结果分析的色块图，进行CombretastatinA-4类似物新分子设计。用所建的模型来预测新分子的活性；对新分子进行分子对接，观察它们与受体蛋白结合打分值和形成氢键个数。31507
毕业论文关键词: CA-4；SYBYL-X 2.0；3D-QSAR；MCF-7；分子对接；药效团；虚拟筛选
The design of new antitumor like CombretastatinA - 4
Based on the molecular docking and QSAR 
Abstract:Cancer in modern human life, often threaten human's life, affecting human health and quality of life, endanger the human's death. Therefore, development of new antitumor drugs is one of the ways to resist cancer. CombretastatinA - 4 from South African shrub extract active component, has a highly effective antitumor activity. In this paper, through the study of analogue CombretastatinA - 4 to study the growth inhibition of breast cancer MCF - 7 based computer aided drug design software SYBYL-X 2.0, according to the collected data to establish reasonable 3D-QSAR model, by molecular docking, pharmacophore virtual screening, design effective anti-tumor CombretastatinA - 4 new analogues to inhibit breast cancer MCF - 7 cell toxicity. Using three-dimensional quantitative structure-activity relationship (3D-QSAR) method to establish the forecast model, with a method (leave one out, LOO) test the credibility of the prediction model is established, and a comparative molecular position analysis model of cross validation coefficient q2 = 0.832, correlation coefficient R2 = 0.993, the standard deviation is 0.133, F value of 583.114.Comparative molecular similarity coefficient analysis model of cross validation q2 = 0.660, the correlation coefficient R2 = 0.984, the standard deviation is 0.195, the F value of 298.843.With the ability to predict the forecast model on the test set further validation. Research results show that the established 3D-QSAR model was statistically with clear and good prediction ability. At the same time the pharmacophore recognition and virtual screening. According to the model of CoMFA and CoMISA result analysis, color piece figure, analogue CombretastatinA - 4 new molecular design. Using the built model to predict the activity of new molecules, of new molecular molecular docking, observe them with receptor proteins play score and the formation of hydrogen bond number.
Keywords: CombretastatinA-4；SYBYL-X 2.0；3D-QSAR；MCF-7；Molecular docking；Pharmacophore；Virtual screening
 目录
1 前言    1
1.1研究的背景与目的    1
1.2研究的历史与现状    2
1.3 主要研究内容    3
1.3.1 分子结构的搭建与优化    3 基于分子对接和QSAR的新型抗肿瘤CombretastatinA-4类似物的设计:http://www.youerw.com/yixue/lunwen_27698.html