Theoretical study of 3-D molecular similarity and ligand binding modes of orthologous human and rat D2 dopamine receptors

The D2 dopamine receptor (D2DR) is an important target for the treatment of some central nervous system disorders, such as Parkinson disease, schizophrenia and drug-dependence. In this work, we built 3-D models of the long form of human and rat D2DRs by considering data from the crystallized D3 dopamine receptor, β2 adrenoceptor and A2a adenosine receptor as templates. Then, docking was performed with ligand and protein residue flexibility. These results were used to analyze ligand recognition and estimate binding affinity. Our results show that the predicted ligand affinity correlates with experimental data, and binding modes are very similar between the D2DRs of these two species.