摘要
采用同源模建的方法构建了A1腺苷受体的三维结构,并与拮抗剂分子DPCPX对接,将得到的复合物结构进行5 ns的分子动力学模拟,以最后2 ns的平均结构和平衡后抽取的11帧构象共12个蛋白结构为研究对象,用包含52个活性分子和1000个诱饵分子的测试库,分别通过DOCK、VINA和GOLD三种对接软件进行评价,最终得出合理的蛋白质模型.根据top10%的富集因子(EF)和ROC曲线下面积(AU-ROC)的计算结果,我们认为GOLD是最适合A1腺苷受体的对接软件,而12个蛋白质结构中F5和Favg的三维结构模型比较合理,可以作为进一步大规模虚拟筛选的模型.
A three dimensional structure model of the adenosine A1 receptor was built using homology modeling.The antagonist DPCPX was docked into the model protein to form a receptor-ligand complex.A molecular dynamics simulation over 5 ns was performed for this complex.We selected 12 protein structures,including the average structure obtained from the last 2 ns of the simulation and 11 frames extracted after equilibration for the study.A database comprising 52 active antagonists and 1000 decoys was then docked into the 12 protein models using DOCK,VINA,and GOLD software packages and these molecules were ranked by their docking scores.The best model protein with the highest enrichment factor（EF） and the largest area under the ROC（AU-ROC） was chosen for further study.The results from the enrichment factor at 10% of the ranked database（EF10） and AU-ROC calculations indicate that GOLD is the best virtual screening software for the adenosine A1 receptor.GOLD docking results suggest that optimized adenosine A1 receptor protein structures,Favg and F5,can be used for virtual screening and for novel design to discover more potent antagonists.
出处
《物理化学学报》
SCIE
CAS
CSCD
北大核心
2010年第10期2833-2839,共7页
Acta Physico-Chimica Sinica
基金
国家科技重大专项关键技术基金(2009ZX09501-002)资助项目~~
关键词
分子动力学模拟
A1腺苷受体
同源模建
GOLD
虚拟筛选
Molecular dynamics simulation
Adenosine A1 receptor
Homology modeling
GOLD
Virtual screening
