趋化因子CCR2的同源模建、分子对接和3D-QSAR研究

Homology Modeling,Molecular Docking and 3D-QSAR Analysis of CCR2

趋化因子CCR2参与炎症反应、免疫移植排斥和肿瘤的发生,已成为新的研究热点。本文以CCR5的晶体结构为模板,同源模建CCR2的结构,并用CCR2小分子抑制剂与其进行分子对接以得到小分子的最优构象。在对接叠合的基础上建立了QSAR模型,采用比较分子场分析(Co MFA)以及比较分子相似性分析(Co MSIA)研究得到Co MFA和Co MSIA模型最佳评价参数分别为q2=0.743,r2=0.968和q2=0.68,r2=0.978。3D-QSAR模型的等势图分析表明,改造配体R3基团可提高化合物活性。所建模型稳定性好、预测性强,对基于CCR2的小分子抑制剂的设计、优化和改造提供了参考。

CCR2 plays an important role in aspects of inflammation,transplantation immune rejection and tumor formation. It has become a new biological treatment target. Based on using crystal structure of CCR5 as template,homologous model of CCR2 was built,then docking with small molecule inhibitors to get the optimum configuration of small molecule. The best evaluation parameters of comparative molecular field analysis（ Co MFA） and comparative molecular similarity analysis（ Co MSIA） models are q^2= 0. 743,r^2= 0. 968 and q^2= 0. 68,r^2= 0. 978,respectively.Through analyzing the potential diagram of 3D-QSAR models,we may safely draw the conclusion that modification on R3 groups can improve the activity of the compound. The established model has a strong ability of prediction. This paper may provide a reference for design,optimization and transformation of small molecule inhibitors CCR2.