Multi-conformation dynamic pharmacophore modeling of the peroxisome proliferator-activated receptor γ for the discovery of novel agonists
| Autor: | Songmi Kim, Young-sik Sohn, Yuno Lee, Keun Woo Lee, Yongseong Kim, Sundarapandian Thangapandian, Jung-Keun Suh, Chanin Park, Hyong-Ha Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Amino Acid Motifs
Peroxisome proliferator-activated receptor Computational biology Molecular Dynamics Simulation Rosiglitazone Small Molecule Libraries Drug Discovery Materials Chemistry Cluster Analysis Humans Physical and Theoretical Chemistry Receptor Spectroscopy chemistry.chemical_classification Virtual screening Binding Sites Hydrogen Bonding Peroxisome Computer Graphics and Computer-Aided Design Combinatorial chemistry Molecular Docking Simulation PPAR gamma chemistry Thiazolidinediones Pharmacophore Protein Binding |
| Zdroj: | Journal of molecular graphicsmodelling. 46 |
| ISSN: | 1873-4243 |
| Popis: | Activation of the peroxisome proliferator-activated receptor γ (PPARγ) is important for the treatment of type 2 diabetes and obesity through the regulation of glucose metabolism and fatty acid accumulation. Hence, the discovery of novel PPARγ agonists is necessary to overcome these diseases. In this study, a newly developed approach, multi-conformation dynamic pharmacophore modeling (MCDPM), was used for screening candidate compounds that can properly bind PPARγ. Highly populated structures obtained from molecular dynamics (MD) simulations were selected by clustering analysis. Based on these structures, pharmacophore models were generated from the ligand-binding pocket and then validated to check the rationality. Consequently, two hits were retrieved as final candidates by utilizing virtual screening and molecular docking simulations. These compounds can be used in the design of novel PPARγ agonists. |
| Databáze: | OpenAIRE |
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