基于计算机模拟的QSAR模型和分子对接模型的研究环境内分泌干扰物和人体内受体的结合作用.docVIP

基于计算机模拟的QSAR模型与分子对接模型研究环境内分泌干扰物与人体内受体的结合作用 刘建昌 兰州大学药学院, 甘肃 兰州 730000 摘要： 研究目的 通过计算机分子模拟的方法研究环境内分泌干扰物（EDC）小分子与相应蛋白质受体结合的过程，解释EDC在体内的作用机制。 研究内容 1）针对环境中出现的大量内分泌干扰物，建立其与相应受体结合的结合亲和力的二维预测模型；建立模型的方法包括线性的多元线性回归方法和非线性的支持向量机方法； 2）用对接方法研究内分泌干扰物EEDs与体内激素受体的结合过程和作用机制；分析受体与配体结合部位的氨基酸序列、氢键形成、静电作用以及疏水口袋等多方面的信息。 结论 本工作应用多元线性回归方法支持向量机方法分别建立了146个内分泌干扰物与结合亲合力的定量预测模型。通过预测模型之间的比较，证明非线性的SVM 模型有最好的预测能力。由此我们可以得出下面的结论：（1）所提出的模型可以从分子水平上识别和提供内分泌干扰物与受体结合有关的结构特征；（2）氢键是影响化合物与受体结合的最主要因素 关键词 内分泌干扰物；定量结构活性关系（QSAR）;分子对接 Molecular docking method and QSAR models for studying Binding Behavior of endocrine disrupting chemicals (EDC) Jian-chang Liu School of Pharmacy, Lanzhou University, Lanzhou 730000, China Abstract Purpose: The two QSAR (MLR model and SVM mode) models and Molecule Docking method were applied in this paper to try to rapidly identify potential androgenic endocrine disrupting compounds and estrogen endocrine disrupting chemicals. (1) Two methods, MLR and SVM, were used to construct linear and nonlinear QSARs to predict AR and ER binding of structurally diverse chemicals. (2) Molecule Docking method is also used in this paper to modeling the behavior of EDCs ligands binding to corresponding protein receptors. Conclusion: (1) The two resultant QSAR models were compared with respect to statistical measures from a leave-one-out process, with SVM yielding the best model performance in terms of self-consistency and ability to predict the activity of the test chemicals. (2）It indicates that the hydrogen bonding interactions may be the most relevant factor controlling the binding behavior, affecting the space-matching between the AR protein and the ligand. Thus, the result of QSAR models and docking study can give us some insight into the factors that govern the binding behavior for these specific chemicals. In turn, this knowledge could be used to develop in silico predictive toxicology models to rapidly identify potential androgenic EDCs. Keywords Endocrine Disruptors Chemicals (EDC);