Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model
Abstract
Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately-as is true of most GPCRs-no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.
Keywords:
Dopamine / Molecular modeling / Arylpiperazine / Docking simulationsSource:
Journal of Molecular Modeling, 2013, 19, 4, 1751-1762Publisher:
- Springer, New York
Funding / projects:
- Modeling and Numerical Simulations of Complex Many-Body Systems (RS-171017)
- Structure-activity relationship of newly synthesized biological active compound (RS-172032)
- European Commission
DOI: 10.1007/s00894-012-1731-6
ISSN: 1610-2940
PubMed: 23300056
WoS: 000316677600027
Scopus: 2-s2.0-84876408838
Collections
Institution/Community
IHTMTY - JOUR AU - Šukalović, Vladimir AU - Šoškić, Vukić AU - Senćanski, Milan AU - Andrić, Deana AU - Kostić Rajačić, Slađana PY - 2013 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1349 AB - Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately-as is true of most GPCRs-no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors. PB - Springer, New York T2 - Journal of Molecular Modeling T1 - Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model VL - 19 IS - 4 SP - 1751 EP - 1762 DO - 10.1007/s00894-012-1731-6 ER -
@article{ author = "Šukalović, Vladimir and Šoškić, Vukić and Senćanski, Milan and Andrić, Deana and Kostić Rajačić, Slađana", year = "2013", abstract = "Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately-as is true of most GPCRs-no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.", publisher = "Springer, New York", journal = "Journal of Molecular Modeling", title = "Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model", volume = "19", number = "4", pages = "1751-1762", doi = "10.1007/s00894-012-1731-6" }
Šukalović, V., Šoškić, V., Senćanski, M., Andrić, D.,& Kostić Rajačić, S.. (2013). Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model. in Journal of Molecular Modeling Springer, New York., 19(4), 1751-1762. https://doi.org/10.1007/s00894-012-1731-6
Šukalović V, Šoškić V, Senćanski M, Andrić D, Kostić Rajačić S. Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model. in Journal of Molecular Modeling. 2013;19(4):1751-1762. doi:10.1007/s00894-012-1731-6 .
Šukalović, Vladimir, Šoškić, Vukić, Senćanski, Milan, Andrić, Deana, Kostić Rajačić, Slađana, "Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model" in Journal of Molecular Modeling, 19, no. 4 (2013):1751-1762, https://doi.org/10.1007/s00894-012-1731-6 . .