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5-HT1A是治疗焦虑症、抑郁症和疼痛等精神类疾病的重要靶点.近年来寻找5-HT1A受体配体以及相关药物的发现,一直是研究的热点.本文首先采用同源模建的方法构建了一个5-HT1A受体模型,并通过与MP349进行分子对接研究,得到了一个可靠的受体-配体结合模式.在此基础上,建立了一个基于受体的药效团模型,该药效团模型包含许多配体和受体相互作用的重要特征;并在后续的虚拟筛选实验中验证了这个药效团模型检验真正的5-HT1A受体配体的能力.本研究结果可用于指导今后5-HT1A>配体的合成改造以及新的先导化合物的发现.“,”5-HT1A receptor is a crucial therapeutic target for the treatment of anxiety, depression, pain, etc. Design and preparation of potent 5-HT1A receptor ligands for drug discovery has attracted extensive attention in the past few years. In this paper, a three dimensional model of human 5-HT1A receptor was constructed by means of homology modeling. And the docking of MP349 to the receptor suggested a reliable binding mode for 5-HT1A receptor ligand. Based on this ligand-receptor binding mode, an elaborate receptor structure based pharmacophore model was established, which revealed many important features responsible for ligand and 5-HT1A receptor interactions. A virtual screening experiment verified the ability of this pharmacophore model to discover true 5-HT1A receptor ligand. The results of this research would provide important information for further optimizations of 5-HT1A receptor ligands and guide related new lead discoveries.