Modeling the Similarity and Divergence of Dopamine D2-like Receptors and Identification of Validated Ligand-Receptor Complexes

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Böckler F, Lanig H, Gmeiner P
Zeitschrift: Journal of Medicinal Chemistry
Verlag: American Chemical Society
Jahr der Veröffentlichung: 2005
Band: 48
Seitenbereich: 694-709
ISSN: 0022-2623
Sprache: Englisch


Abstract


Focusing on the similarity and divergence of GPCR subtypes and their ligand interactions, we generated dopamine D2, D3, and D 4 receptor models based on the rhodopsin crystal structure and refined these with an extensive MM/MD protocol. After validation by diagnostic experimental data, subtype-specific relative positions of TM1, 2, 6, and 7 and bending angles of TM7 were found. To sample the conformational space of the complex, we performed simulated-annealing runs of the receptor protein with the sub-nanomolar antagonist spiperone. Docking a representative set of ligands, we were able to identify one superior model for each subtype when excellent correlations between predicted energies of binding and experimental affinities (r2 = 0.72 for D2, 0.91 for D3 and 0.77 for D4) could be observed. Further analysis revealed general ligand interactions with ASP3.32 and aromatic residues in TM6/7 and individual key interactions with TM1 and TM2 residues of the D3 and D4 receptor models, respectively.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Lanig, Harald PD Dr.
Exzellenz-Cluster Engineering of Advanced Materials


Zitierweisen

APA:
Böckler, F., Lanig, H., & Gmeiner, P. (2005). Modeling the Similarity and Divergence of Dopamine D2-like Receptors and Identification of Validated Ligand-Receptor Complexes. Journal of Medicinal Chemistry, 48, 694-709. https://dx.doi.org/10.1021/jm049612a

MLA:
Böckler, Frank, Harald Lanig, and Peter Gmeiner. "Modeling the Similarity and Divergence of Dopamine D2-like Receptors and Identification of Validated Ligand-Receptor Complexes." Journal of Medicinal Chemistry 48 (2005): 694-709.

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Zuletzt aktualisiert 2018-09-08 um 11:53