scholarly journals A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Receptor α

ChemMedChem ◽  
2017 ◽  
Vol 12 (16) ◽  
pp. 1399-1407 ◽  
Author(s):  
Ugo Perricone ◽  
Marcus Wieder ◽  
Thomas Seidel ◽  
Thierry Langer ◽  
Alessandro Padova ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Virtual Screening ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Sulfonylureas and Glinides Exhibit Peroxisome Proliferator-Activated Receptor γ Activity: A Combined Virtual Screening and Biological Assay Approach

2006 ◽  
Vol 71 (2) ◽  
pp. 398-406 ◽  
Author(s):  
Marco Scarsi ◽  
Michael Podvinec ◽  
Adrian Roth ◽  
Hubert Hug ◽  
Sander Kersten ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Biological Assay ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals In SilicoIdentification of Potent PPAR-γAgonists from Traditional Chinese Medicine: A Bioactivity Prediction, Virtual Screening, and Molecular Dynamics Study

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Molecular Dynamics ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Virtual Screening ◽  
Prediction Models ◽  
Protein Complexes ◽  
Md Simulations ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
Key Residues

The peroxisome proliferator-activated receptors (PPARs) related to regulation of lipid metabolism, inflammation, cell proliferation, differentiation, and glucose homeostasis by controlling the related ligand-dependent transcription of networks of genes. They are used to be served as therapeutic targets against metabolic disorder, such as obesity, dyslipidemia, and diabetes; especially, PPAR-γis the most extensively investigated isoform for the treatment of dyslipidemic type 2 diabetes. In this study, we filter compounds of traditional Chinese medicine (TCM) using bioactivities predicted by three distinct prediction models before the virtual screening. For the top candidates, the molecular dynamics (MD) simulations were also utilized to investigate the stability of interactions between ligand and PPAR-γprotein. The top two TCM candidates, 5-hydroxy-L-tryptophan and abrine, have an indole ring and carboxyl group to form the H-bonds with the key residues of PPAR-γprotein, such as residues Ser289 and Lys367. The secondary amine group of abrine also stabilized an H-bond with residue Ser289. From the figures of root mean square fluctuations (RMSFs), the key residues were stabilized in protein complexes with 5-Hydroxy-L-tryptophan and abrine as control. Hence, we propose 5-hydroxy-L-tryptophan and abrine as potential lead compounds for further study in drug development process with the PPAR-γprotein.

scholarly journals Development of a Protocol for Virtual Screening of PPARγ Weak Partial Agonists and Their Metabolites: Case Study on Naturally-derived Oleanane Triterpenoids

2021 ◽  
Vol 25 (2) ◽  
pp. 117-132
Author(s):  
Merilin Al Sharif ◽  
◽  
Petko Alov ◽  
Vessela Vitcheva ◽  
Antonia Diukendjieva ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Molecular Mechanisms ◽  
Partial Agonist ◽  
Mechanistic Explanation ◽  
Binding Mode ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Agonists ◽  
Docking Protocol ◽  
Agonistic Activity

Triterpenoids are well known metabolic syndrome (MetS) modulators. One of the suggested molecular mechanisms of action involves peroxisome proliferator-activated receptor gamma (PPARγ) activation. In this study we aimed to: (i) develop a virtual screening (VS) protocol for PPARγ weak partial agonists, (ii) predict potential metabolic transformations of naturally-derived triterpenoids, and (iii) perform VS of the triterpenoids and their metabolites. The NIH PubMed system was searched for publications about naturally-derived oleanane triterpenoids which are agonists or up-regulators of PPARγ. Structure- and ligand-based methods were combined in the development of the VS protocol. Metabolites were predicted using Meteor Nexus expert system (Lhasa Limited). Two in-house virtual libraries of PPARγ weak partial agonists and naturally-derived triterpenoids with their predicted metabolites were compiled. The pharmacophore-based docking protocol was applied for VS of the collected triterpenoids. Most of the docking poses reproduced the binding mode of caulophyllogenin (a weak partial agonist) in a complex with PPARγ (PDB ID 5F9B). Our results contribute to the mechanistic explanation of the effects of triterpenoids suggesting possible weak partial agonistic activity toward PPARγ. This research can direct further studies on triterpenoids’ role in MetS modulation. The developed protocol can be applied for VS of any PPARγ weak partial agonists.

scholarly journals Virtual Screening as a Technique for PPAR Modulator Discovery

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Stephanie N. Lewis ◽  
Josep Bassaganya-Riera ◽  
David R. Bevan
Keyword(s):  
Virtual Screening ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Effective Means ◽  
Binding Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Compound Libraries ◽  
Computational Screening ◽  
Reporter Assays

Virtual screening (VS) is a discovery technique to identify novel compounds with therapeutic and preventive efficacy against disease. Our current focus is on the in silico screening and discovery of novel peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. It is well recognized that PPARγagonists have therapeutic applications as insulin sensitizers in type 2 diabetes or as anti-inflammatories. VS is a cost- and time-effective means for identifying small molecules that have therapeutic potential. Our long-term goal is to devise computational approaches for testing the PPARγ-binding activity of extensive naturally occurring compound libraries prior to testing agonist activity using ligand-binding and reporter assays. This review summarizes the high potential for obtaining further fundamental understanding of PPARγbiology and development of novel therapies for treating chronic inflammatory diseases through evolution and implementation of computational screening processes for immunotherapeutics in conjunction with experimental methods for calibration and validation of results.

scholarly journals Computational identification of potential chemoprophylactic agents according to dynamic behavior of peroxisome proliferator-activated receptor gamma

RSC Advances ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 147-159
Author(s):  
Zhiwei Yang ◽  
Yizhen Zhao ◽  
Dongxiao Hao ◽  
He Wang ◽  
Shengqing Li ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Dynamic Behavior ◽  
Screening Procedure ◽  
Peroxisome Proliferator ◽  
Targeted Therapeutics ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Strategy ◽  
Conformational Plasticity ◽  
Computational Identification

Offering a new strategy for resurrecting PPARγ-targeted therapeutics to chemoprevention, by taking the conformational plasticity of the receptor into account in the virtual screening procedure.

Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPARα) as a case study

2013 ◽  
Vol 44 (1) ◽  
pp. 1-49 ◽  
Author(s):  
J. Christopher Corton ◽  
Michael L. Cunningham ◽  
B. Timothy Hummer ◽  
Christopher Lau ◽  
Bette Meek ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Peroxisome Proliferator ◽  
Framework Analysis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha
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