Multiple templates-based homology modeling and docking analysis of angiotensin II type 1 receptor

XIE Yun-feng(谢云丰), JIANG Yu-ren(蒋玉仁), PAN Ya-fei(潘亚飞), CHEN Dan(陈丹), LI Chuan-jun(李传俊)

(College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China)

Abstract:Using the latest reported homologous Chemokine receptors (PDB ID: 3ODU, 3OE0 and 3OE6) as templates, twenty models of angiotensin II (Ang II) type 1 (AT1) receptor (known as p30556) were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic (MD) simulation for model 0020 was conducted in normal saline (0.9%, w/V) under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers (ARBs). The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-π interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design.

Key words:angiotensin II type 1 receptor; docking; homology modeling; molecular dynamics