Citation: KE Yan-Rong, JIN Hong-Wei, LIU Zhen-Ming, ZHANG Liang-Ren. Homology Modeling and Structure Validation of the Adenosine A₁ Receptor[J]. Acta Physico-Chimica Sinica, ;2010, 26(10): 2833-2839. doi: 10.3866/PKU.WHXB20100916 shu

Homology Modeling and Structure Validation of the Adenosine A₁ Receptor

1.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China

Received Date: 19 May 2010
Available Online: 27 September 2010

A three dimensional structure model of the adenosine A₁ receptor was built using homology modeling. The anta nist 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 anta nists and 1000 decoys was then docked into the 12 protein models using DOCK, VINA, and LD 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 LD is the best virtual screening software for the adenosine A₁ receptor. LD 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 anta nists.
- Molecular dynamics simulation,
- Adenosine A₁ receptor,
- Homology modeling,
- LD,
- Virtual screening
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沈阳化工大学材料科学与工程学院沈阳 110142

Homology Modeling and Structure Validation of the Adenosine A1 Receptor

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通讯作者: 陈斌, bchen63@163.com

Homology Modeling and Structure Validation of the Adenosine A₁ Receptor