Open AccessModeling key interactions between dopamine D2 receptor second extracellular loop and arylpiperazine ligands
Author(s) -
Vladimir Šukalović,
Vukić Šoškić,
Deana Andrić,
Goran Roglić,
Sladjana KostićRajačić
Publication year - 2012
Publication title -
journal of the serbian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.227
H-Index - 45
eISSN - 1820-7421
pISSN - 0352-5139
DOI - 10.2298/jsc111028212s
Subject(s) - dopamine receptor d2 , chemistry , pharmacophore , dopaminergic , g protein coupled receptor , docking (animal) , ligand (biochemistry) , receptor , rhodopsin , transmembrane domain , stereochemistry , biophysics , biochemistry , combinatorial chemistry , dopamine , neuroscience , biology , medicine , retinal , nursing
Second extracellular loop (ecl2) of dopamine (DA) D2 receptor is an essential part of dopaminergic ligands binding pocket. To form a part of the ligand binding surface it has to fold down into the transmembrane domain of the DA receptor. The current study describes the modeling of the D2 DA receptor ecl2 and its interactions with arylpiperazine ligands. In order to model D2 DA receptor ecl2, the number of arylpiperazine ligands was used to propose pharmacophore model. D2 DA receptor ecl2 model was built using Accelrys Discovery Studio. To test the proposed model, docking analysis was performed and key amino acid residues were determined. Proposed receptor-ligand iteractions were rationalized and compared with measured binding affinity. It is shown that D2 DA receptor ecl2 significantly participates in receptor-ligand complex formation through aromatic, hydrophobic and polar interaction. Taking them in account would benefit GPCR molecular modeling and facilitate the design of novel active compounds