Modeling the Similarity and Divergence of Dopamine D2-like Receptors and Identification of Validated Ligand-Receptor Complexes
Böckler F, Lanig H, Gmeiner P (2005)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2005
Journal
Publisher: American Chemical Society
Book Volume: 48
Pages Range: 694-709
DOI: 10.1021/jm049612a
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.
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How to cite
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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