| 刘蒙蒙,丁雪垒,周朋朋,舒茂,林治华.化学通报,2016,79(9):844-851. |
| 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 |
| 投稿时间：2016-03-03 修订日期：2016-03-28 |
| DOI： |
| 中文关键词: CCR2 同源模建 分子对接 3D-QSAR |
| 英文关键词:3D-QSAR homology modeling molecular docking CCR2 |
| 基金项目:国家自然科学基金项目（81171508）; 重庆市自然科学基金重点项目(CSTC 2013 JJB10004)；重庆市教委科技项目(KJ1500943，KJ1400946) |
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| 中文摘要: |
| 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（CoMFA)以及比较分子相似性分析（CoMSIA)研究得到CoMFA和CoMSIA模型最佳评价参数分别为q2=0.743，r2=0.968和q2=0.68，r2=0.978。通过分析3D-QSAR模型的等势图得出改造配体R3基团可提高化合物活性。所建模型稳定性好、预测性强，对CCR2相关疾病药物的设计、优化和改造提供了参考。 |
| 英文摘要: |
| 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 the crystal structure of CCR5 as template, homologous model the structure of CCR2.Then docking with small molecule inhibitors to get the optimum configuration of small molecule .Then build a QSAR model,which result to CCR2 receptor inhibitors form hydrogen bonds with ARG176 residues, formππbond with ARG176,TYR229 residues. Using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA). We get the best evaluation parameters of CoMFA and CoMSIA is q2 = 0.743 ,r2 = 0.968 and q2 = 0.68 , r2 = 0.978. Through analysis potential diagram of 3D-QSAR models,we get a conclusion that transform R3 groups may enhance the activity of the compound .The model has a strong ability of prediction.The paper may provide a reference for the Small molecule compound of CCR2 inhibitors design, optimization and transformation. |
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