Molecular modeling of interactions between tetrahydroprotoberberines and dopamine receptors.
OBJECTIVE
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.


CONCLUSIONS
Our ligand-receptor interaction models should be helpful for rational design of more potent drugs.
Tang
Y
Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Chen
K X
KX
Jiang
H L
HL
Jin
G Z
GZ
Ji
R Y
RY
D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry; D001600:Berberine Alkaloids / Q000737:chemistry; D001665:Binding Sites; D018492:Dopamine Antagonists / Q000737:chemistry; D004347:Drug Interactions; D008956:Models, Chemical; D008969:Molecular Sequence Data; D017447:Receptors, Dopamine D1 / Q000737:chemistry / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism
D001600:Berberine Alkaloids; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001599:Berberine; C010513:stepholidine; D001436:Bacteriorhodopsins; C014845:berbine