摘要干扰运输过程是内分泌干扰物（EDCs）扰乱内分泌功能的一个重要途径。然而现阶段的研究中，相比于与激素受体结合和合成酶的过程，这一机制尤其是性激素的转运过程并没有得到足够的关注。本研究基于经济合作与发展组织（OECD）关于定量-活性关系（QSAR）模型构建与使用导则，建立了内分泌干扰物和两种鱼类性激素转运蛋白结合能力（log RBA）的预测模型。其中，对虹鳟鱼的相关数据建立了定性的分类模型，对斑马鱼的相关数据通过多元线性回归方法建立了QSAR模型。统计结果表明，该模型具有良好的拟合度、稳健性和预测能力。采用欧几里得距离法和威廉姆斯图表征了模型的应用域，并对模型进行了机理解释，讨论了影响EDC与鱼性激素转运蛋白结合能力的主要因素。73650

毕业论文关键词  相对结合能力  鱼性激素转运蛋白  QSAR模型  分类模型

毕业设计说明书外文摘要

Title  Development of Predictive Model for Predicting Binding Affinity of Endocrine Disrupting Chemicals to Fish Sex Hormone-Binding Globulin                     

Abstract Disturbing the transport process is a crucial pathway for endocrine disrupting chemicals (EDCs) exerting disrupting endocrine function。 However, this mechanism did not deserve enough attention comparing with that of hormones receptors and synthetase up to now, especially for the sex hormone transport process。 In this present study, optimal classification models or QSAR models for predicting the binding activity of EDCs to two fishes SHBGs, were established and validated following the OECD guidelines。 A qualitative classification model was established for the related data of rainbow trout。 The QSAR quantitative model was established for the related data of Zebrafish by multiple linear regression method。 Statistical results indicated that the models had satisfactory goodness of fit, robustness and predictive ability。 The applicability domain (AD) of the models was characterized by the Euclidean distance-based method or Williams plot。 Then, the mechanism of the model was explained, and the main factors that affect the binding ability of EDCs and the sex hormone transporter were also discussed。

Keywords  Relative binding affinity (RBA)  Fish sex hormone-binding globulin (fSHBG)  Quantitative structure-activity relationship (QSAR)  Classification model

目   次

1　绪论 1

1。1　环境内分泌干扰物 1

1。2　虹鳟鱼及斑马鱼 2

1。3　QSAR模型 3

1。4　研究的内容与意义 5

2　材料与方法 6

2。1　数据集 6

2。2　分子描述符的计算 10

2。3　模型的建立与验证 10

2。4　模型的应用域 11

3　虹鳟鱼的分类模型 12

3。1　分类模型及描述符解释 12

3。2　应用域的评价 12

3。3　机理解释 13

4　斑马鱼的QSAR定量模型 15

4。1　QSAR定量模型及描述符解释 15

4。2　应用域的评价 16

4。3　机理解释