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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。
Chemokine CCR2 is involved in inflammatory reactions, immune graft rejection and tumorigenesis, and has become a new research hotspot. In this paper, the crystal structure of CCR5 was used as a template to construct the CCR2 structure by homology modeling, and the CCR2 small molecule inhibitor was used for molecular docking to obtain the optimal conformation of the small molecule. The QSAR model was established on the basis of docking and overlap. CoMFA and Co MSIA showed that the optimal evaluation parameters of Co MFA and Co MSIA were q2 = 0.743, r2 = 0.968 and q2 = 0.68, r2 = 0.978. Analysis of the isoelectric point diagrams of the D-QSAR model shows that the modification of the ligand R3 group can increase the activity of the compound. The model has good stability and strong predictive power, which provides references for the design, optimization and modification of CCR2-based small molecule inhibitors.