Modeling key interactions between dopamine D2 receptor second extracellular loop and arylpiperazine ligands

Journal of the Serbian Chemical Society

卷:77

关键词: extracellular loop;    dopamine;    arylpiperazine;    molecular modeling;    GPRC;   

DOI  :  10.2298/JSC111028212S

来源: DOAJ

【 摘 要 】

Second extracellular loop (ecl2) of dopamine (DA) D2 receptor is an essentialpart of dopaminergic ligands binding pocket. To form a part of the ligandbinding surface it has to fold down into the transmembrane domain of the DAreceptor. The current study describes the modeling of the D2 DA receptorecl2 and its interactions with arylpiperazine ligands. In order to model D2DA receptor ecl2, the number of arylpiperazine ligands was used to proposepharmacophore model. D2 DA receptor ecl2 model was built using AccelrysDiscovery Studio. To test the proposed model, docking analysis was performedand key amino acid residues were determined. Proposed receptor-liganditeractions were rationalized and compared with measured binding affinity.It is shown that D2 DA receptor ecl2 significantly participates inreceptor-ligand complex formation through aromatic, hydrophobic and polarinteraction. Taking them in account would benefit GPCR molecular modelingand facilitate the design of novel active compounds.

【 授权许可】

Unknown