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OALib Journal期刊
ISSN: 2333-9721
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分子动力学模拟、结合自由能计算和3d-qsar研究大麻ii型受体和其激动剂的相互作用
, PP. 1436-1449
Keywords: cb2,激动剂,分子动力学模拟,结合自由能,3d-qsar
Abstract:
cb2是一类主要表达于人体免疫系统的g蛋白偶联受体,已成为研发治疗免疫系统疾病药物的良好靶点。本论文基于cb2同源蛋白模型,结合分子对接和分子力学/分子动力学模拟研究cb2与其激动剂复合物在磷脂双分子层膜体系dppc/tip3p中的三维结构模型,分别运用mm-pbsa和mm-gbsa方法计算结合自由能和能量分解。计算结果表明,cb2与其配体的主要结合作用力是范德华力,关键性氨基酸phe197对于结合选择性激动剂至关重要。另外,以分子动力学模拟得到的激动剂稳定构象为模板,运用comfa方法建立相应的三维定量构效关系模型。结合分子模拟得到的作用模式和3d-qsar模型提供的活性结构特征将有助于指导设计新型、高效的cb2选择性激动剂。
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