Ligand-guided homology modeling drives identification of novel histamine H3 receptor ligands

In this study, we report a ligand-guided homology modeling approach allowing the analysis of relevant binding site residue conformations and the identification of two novel histamine H3 receptor ligands with binding affinity in the nanomolar range. The newly developed method is based on exploiting a...

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Bibliographic Details
Published in:PloS one 2019-06, Vol.14 (6), p.e0218820-e0218820
Main Authors: Schaller, David, Hagenow, Stefanie, Stark, Holger, Wolber, Gerhard
Format: Article
Language:English
Subjects:
Algorithms
Binding sites
Biology and Life Sciences
Chemistry
Crystal structure
Drug Evaluation, Preclinical
HEK293 Cells
Histamine
Histamine H3 receptors
Homology
Humans
Lead compounds
Ligands
Medical research
Modelling
Models, Molecular
Molecular Docking Simulation
Novels
Obesity
Pharmaceutical sciences
Pharmacy
Physical Sciences
Protein Binding
Proteins
Radioligand Assay
Receptors
Receptors, Histamine H3 - chemistry
Receptors, Histamine H3 - metabolism
Research and Analysis Methods
Structural Homology, Protein
Structure-Activity Relationship
Three dimensional models
User-Computer Interface
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Summary:In this study, we report a ligand-guided homology modeling approach allowing the analysis of relevant binding site residue conformations and the identification of two novel histamine H3 receptor ligands with binding affinity in the nanomolar range. The newly developed method is based on exploiting an essential charge interaction characteristic for aminergic G-protein coupled receptors for ranking 3D receptor models appropriate for the discovery of novel compounds through virtual screening.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0218820