Original Article

Molecular modeling of interactions between tetrahydroprotoberberines and dopamine receptors

Yun Tang, Kai-Xian Chen, Hua-Liang Jiang, Guo-Zhang Jin, Ru-Yun Ji


"AIM: To build up the structure models of dopamine receptors, then combined with the receptor models, to investigate the action mechanism of tetrahydroprotoberberines (THPB) on dopamine receptors at the molecular level.

METHODS: Using the three-dimensional structure of bacteriorhodopsin as a template, we have constructed dopamine D1 and D2 receptor models on computer. l-Stepholidine was selected as the leading compound of THPB and docked into D1 and D2 receptor active sites.

RESULTS: After manual adjustment and energy minimization, the ligand-receptor interaction models were achieved. Based on these models, the possible action mechanism of THPB on dopamine receptors was suggested that the protonated N atom of THPB form electrostatic interaction and hydrogen-bonding interaction with residue Asp in TM3 of the receptor, the two substituents in D ring of THPB form hydrogen-bonding interactions with two Ser residues in TM5 of the receptor, and the aryl groups form pi-pi interactions with some aryl residues of the receptor around ligand.
CONCLUSION: Our ligand-receptor interaction models should be helpful for rational design of more potent drugs.

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