Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The observed 5-HT1A and alpha1-adrenergic receptor (alpha1-AR) receptor binding properties of a series of 23 thienopyrimidinones were used to develop HASL 3D-QSAR models. A single, low energy conformer of the most active analogue in the series, which was consistent with NMR structural studies, was chosen as a template molecule. Alignments of all the molecules to the template were provided by an Amber/MM2 superposition force field. In this manner, each molecule was represented by five separate low energy conformers which were subsequently used in the generation of HASL 3D-QSAR models. Models derived from multiple conformers were found to exhibit enhanced predictivity compared to models based on single, low energy conformers. In addition, the use of contour imaging of HASL multi-conformer model interactions was found to lead to a more consistent interpretation of those molecular features most significant for 5-HT1A receptor binding.
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PMID:3D-QSAR using 'multiconformer' alignment: the use of HASL in the analysis of 5-HT1A thienopyrimidinone ligands. 1100 86

In the present study experimentally determined ligand selectivity of three methylated buspirone analogues (denoted as MM2, MM5 and P55) towards 5-HT1A and 5-HT2A serotonin receptors was theoretically investigated on a molecular level. The relationships between the ligand structure and 5-HT1A and 5-HT2A receptor affinities were studied and the results were found to be in agreement with the available site-directed mutagenesis and binding affinity data. Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A, each time in a different orientation. Present results were compared with our previous theoretical results, obtained for buspirone and its non-methylated analogues. It was found that due to the presence of the methyl group in the piperazine ring the ligand position alters and the structure of the ligand-receptor complex is modified. Further, the positions of derivatives with pyrimidinyl aromatic moiety and quinolinyl moiety are significantly different at the 5-HT2A receptor. Thus, methylation of such derivatives alters the 3D structures of ligand-receptor complexes in different ways. The ligand-induced changes of the receptor structures were also analysed. The obtained results suggest, that helical domains of both receptors have different dynamical behaviour. Moreover, both location and topography of putative binding sites for buspirone analogues are different at 5-HT1A and 5-HT2A receptors.
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PMID:Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues. 1198 22