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摘要：流感于我国属于多发病症，每年因流感病毒前往医院就诊的患者不在少数。流感属于因流感病毒引起的突发性急性病毒性呼吸道传染疾病。本论文通过研究以扎那米韦为模板的新型神经氨酸酶抑制剂分子来研究对流感病毒的抑制作用。本论文通过运用计算机辅助药物设计软件SYBYL-X 2.0，根据从发表的文献中所收集到的数据建立合理的3D-QSAR模型，根据模型色块图设计出新型的神经氨酸酶抑制剂类似物，并对其进行分子对接等确认其有效性。以三维定量构效关系方法建立了分子预测模型，采用了抽一法检验预测模型的可信性，CoMFA交叉验证系数q2 =0.601，主成分数为6，相关系数R2=0.979标准偏差为0.261，F值为334.506；CoMSIA交叉验证系数q2 =0.580，主成分数为5，相关系数R2=0.964，标准偏差为0.336，F值为238.1429。用测试集进一步验证预测模型的的预测能力的可靠性。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。根据所建模型的CoMFA、CoMISA模型结果分析的色块图，进行扎那米韦类似物新分子设计。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。51109
毕业论文关键词: 扎那米韦；SYBYL-X 2.0；3D-QSAR；H5N1；分子对接；分子设计
Zanamivir as a template of Molecular design of the new neuraminidase inhibitors
Abstract:Influenza in China belong to multiple disease each year because of the flu virus to hospital patients in the minority. The flu is caused by influenza virus sudden acute viral respiratory tract infectious diseases. In this paper through the research to zanamivir for template NEW neuraminidase inhibition agent molecules to study the inhibition of influenza virus. In this paper, by using the computer aided drug design software SYBYL-X 2.0, reasonable 3D-QSAR model is established based on the data collected from the published literature, according to the model of color chart design a new neuraminidase inhibitor analogs, and the of molecular docking indeed Recognize its effectiveness. In a three-dimensional quantitative structure activity relationship methods molecular prediction model was established. By pumping a method to test the prediction model of credibility, CoMFA coefficient of cross validation Q2 =0.601 and scores of 6, correlation coefficient R2=0.979 standard deviation of 0.261., the F value is 334.506; CoMSIA cross validated coefficient Q2 =0.580 and principal component scores of 5, the correlation coefficient R2=0.964, standard deviation is 0.336, F value for 238.1429. test set was also used to further validate the model predictions of the ability to predict the reliability. The results of the study showed that Build 3D-QSAR models in statistics is clear and good predictive ability. According to the models of CoMFA and model CoMISA results analysis of color chart, of zanamivir analogs as new molecular design. By the established model to predict the activity of new molecular; for new molecular docking, observe them with the receptor protein binding scores and the number of hydrogen bonds formed.
Keywords: Zanamivir; SYBYL-X 2; 3D-QSAR; H5N1; molecular docking; molecular design
目录
1 前言 1
1.1 研究的背景与目的 1
1.2 Zanamivir 2
1.3 主要研究内容 3
1.3.1 分子结构的搭建与优化 3
1.3.2 分子的叠合及建立模型、回归分析以及模型分析 3
1.3.3 训练集CoMFA、CoMSIA值、pGI50值预测及新分子的设计