氨基酸突变对GABAa受体结合能力的影响

Studies of Interaction Between GABA and Mutant GABAaR

采用同源建模技术构建了大鼠γ-氨基丁酸a型受体(GABAaR)模型,并将氨基酸残基β157Tyr和β205Tyr突变为相应的突变受体模型.使用分子对接方法计算了γ-氨基丁酸(GABA)与突变前后受体的相互作用.对接计算结果显示,Tyr突变为Phe后,两种突变受体的对接能量大幅提高,GABA生物活性降低;当Phe的对位引入氟原子后,对接能量与未突变受体相比更低.另外,与β205Tyr突变相比,与配体距离较近的β157Tyr突变,对受体与配体作用的影响更大.

Homology modeling and docking are important technologies in computer-aided drug design, which can explain the interactions between ligands and receptors. In this study, a rat γ-aminobutyric acid a-type receptor（GABAaR） model and its β205Tyr and β157Tyr mutant receptor models were built by homology modeling. The interactions between γ-aminobutyric acid （GABA） and the GABAaR and its mutants were studied by molecular docking, and the result show that the docking energy of the mutant receptors increases significantily and the biological activity of GABA decreases when Tyr changes to Phe; the docking energy becomes lower than that of the original receptor when Tyr changes to 4-F-Phe. In addition, the impact of β157Tyr mutations on the interaction between receptors and whenβ157Tyr is closer to the ligand. ligands is much more striking than that of β205Tyr