Polo-Like激酶4(PLK4)抑制剂作为潜在可口服抗癌药的计算机辅助药物设计研究

摘要Polo-Like激酶4(Polo-like kinase 4, PLK4)是Polo-Like蛋白激酶的成员之一，是一种苏氨酸蛋白激酶。Polo-Like激酶4主要在分裂活跃的组织和细胞中表达，它在中心粒复制的过程中起着关键的作用。此外，Polo-Like激酶4与肿瘤发主、发展有着密切的联系。Polo-Like激酶4主要作用在在分裂活跃的组织和细胞中表达，参与中心体复制和成熟，例如DNA损伤的细胞应激反应，细胞周期的调控等生理过程。本篇论文采用3D-QSAR法，主要在SYBYL-X 2.0的技术支持下，以部分分子结构和生物活性即pIC50值，已知的Polo-Like激酶4(PLK4)抑制剂为训练集, 选用此系列的分子立体场、静电场、疏水场、氢键供体场、氢键受体场等各种分子力场，用三文定量构效关系(3D-QSAR) 方法建立反映分子结构与生物活性之间的定量构效关系模型。并基于此模型来设计新的Polo-Like激酶4(PLK4)抑制剂、进行结构修、分子对接和药效团分析。30026
毕业论文关键词：Polo-Like激酶4   抑制剂    三文定量构效关系
The Computer Aided Drug Design of Polo-like kinase 4 inhibitor as Potential peroral Anti-Cancer Drugs
Abstract Polo-like kinase 4 (Polo - like kinase 4, PLK4) is one of the Polo sample protein kinase family members, is a serine/threonine protein kinase. Polo - Like kinase 4 mainly expressed in split active tissues and cells, and it's on the centriole plays a key role in the process of copying. In addition, PLK4 Lord sends with tumor, development has the close relation. PLK4 were found mainly in the pision of active expression in the tissues and cells, may participate in centrosome replication and mature, cell stress response, such as DNA damage, cell cycle regulation and other physiological processes.
    3 D- QSAR method, this paper mainly under the technical support of SYBYL - 2.0 X, in part to the molecular structure and biological activity pIC50 value, namely the Polo known - Like kinase 4 (PLK4) inhibitors as the training set, choose the series of molecular 3 d field, electrostatic field, scanty water yards, hydrogen bond donor, hydrogen bond receptor, games and other molecular force field, with 3 d quantitative structure-activity relationship (3D- QSAR) method to establish reflect between molecular structure and biological activity of quantitative structure-activity relationship model. And based on this model to design the new Polo - Like kinase 4 (PLK4) inhibitors, structure, molecular docking and pharmacophore analysis
关键词：
PLK4         Polo-like kinase 4         3D- QSAR
第一章绪论   1
1.研究的背景与目的   1
2.1 PLK4激酶的结构、表达以及活性调节   1
2.1.1 Polo-Like激酶4的基因和蛋白质结构   1
2.1.2 PLK4激酶的表达调控   2
2.1.3 PLK4激酶的亚细胞定位   2
2.2 PLK4的生物学功能研究   2
2.2.1 PLK4与中心体复制   3
2.2.2 PLK4与肿瘤    3
2.2.3 PLK4与抑制剂   4
2.3定量构效关系的研究   4
1.3 主要研究内容   4
2.3.1 分去子结构的搭建与优化   5
2.3.2 分子的叠合及建立模型、回归分析以及模型分析   5
2.3.3 CoMFA、CoMSIA值分析、新分子的设计   5
2.3.4分子对接   5
2.3.5药效团识别与虚拟筛选   6
2.1 SYBYL软件简介   7
2.2 三文定量构效关系（3D-QSAR）的介绍及其基本原理   7
2.3 研究方法概述   7
2.3.1 化合物活性构象的确定   7 Polo-Like激酶4(PLK4)抑制剂作为潜在可口服抗癌药的计算机辅助药物设计研究:http://www.751com.cn/yixue/lunwen_25520.html