MOLECULAR MODELING OF INTERACTIONS BETWEEN TETRAHYDROPROTOBERBERINES AND DOPAMINE-RECEPTORS

AIM: To build up the structure models of dopamine receptors, then comb ined with the receptor models, to investigate the action mechanism of tetrahydroprotoberberines (THPB) on dopamine receptors at the molecula r level. METHODS: Using the three-dimensional structure of bacteriorho dopsin as a template, we have constructed dopamine D-1 and D-2 recepto r models on computer. l-Stepholidine was selected as the leading compo und of THPB and docked into D-1 and D-2 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 ligan d. CONCLUSION: Our ligand-receptor interaction models should be helpfu l for rational design of more potent drugs.