Combretastain A-4类似物抑制微管蛋白聚合作用的二维定量构效关系研究
关键词：Combretastain A-4类似物；量子化参数；密度泛函理论；定量构效关系；微管蛋白聚合抑制作用
2D-QSAR for Tubulin Polymerization Inhibition of Combretastain A-4 Analogue
Abstract: QSAR is an important research method which is the study of compounds’ Quantitative Structure-Activity Relationship. Based on Density Functional Theory (DFT) method, quantum-chemical parameters of aromatic components in combretastain A-4 analogues were calculated at the level of B3LYP/6-311G* by Gaussian03. While using of ChemBio3D to calculate the physicochemical parameters of aromatic components in Pomelo peel oil. Using SPSS 11.5 program, with the Stepwise and Enter entering parameters mode, the QSAR equation between the calculated quantum chemistry structural parameters and the physic-chemical parameters and combretastain A-4 analogues have been established based on regression analysis (Multivariate Linear Regression). Through checking the accuracy of the model with the newly selected data to verify if the final QSAR model is acceptable, in which ELUMO^2, ClogP and HF are the most important factors on the tubulin polymerization inhibition. The result shows that the QSAR model can predict the tubulin polymerization inhibition of combretastain A-4 analogues effectively.
Key Words： Combretastain A-4 analogue；Quantum-chemical parameter；DFT；QSAR；Tubulin Polymerization Inhibition
目录
1 绪论 1
1.1 研究背景和目的 1
1.1.1 QSAR的简介 1
1.1.2 QSAR研究的发展过程 1
1.2 Combretastain A-4类似物抑制围观蛋白聚合作用的研究现状和进展 2
1.3 研究目的 5
1.4 主要研究内容 6
1.4.1 Combretastain A-4类似物的几何构型的优化 7
1.4.2 Combretastain A-4类似物各量子化学参数和理化参数的计算 7
1.4.3 Combretastain A-4类似物分子结构参数与微管蛋白聚合抑制作用的关系研究 7
1.5 预期达到的研究目标和技术难点 7
2 理论原理和计算方法 8
2.1 理论基础 8
2.1.1量子化学方法基本原理 8
2.1.2半经验计算方法（semi-emperical） 9
2.1.3密度泛函理论[28] 9
2.1.4基组的选择 10
2.1.5计算工具 11
2.2 QSAR中常用的数理统计方法 11
2.2.1 多元线性回归法[31-34] 11
2.2.2 多元线性回归验证方法 11
2.2.3 一次进入法（Enter法） 12
2.2.4多元逐步回归法[39]（Stepwise法） 13
2.3研究方案 13
2.3.1拟采取的研究方法和技术路线 13
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