Document Detail


Interaction models of a series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids against PPARalpha and PPARgamma: molecular modeling and comparative molecular similarity indices analysis studies.
MedLine Citation:
PMID:  19200038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular recognition of a series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids by PPARalpha and PPARgamma was investigated by using molecular modeling and 3D-QSAR analyses. The binding models of these compounds were determined by hydrophobic property analyses and molecular docking procedure FlexX. It was found that the hydrophilic heads of these compounds form four specific conserved hydrogen bonds with the ligand binding pockets of PPARalpha and PPARgamma, which results in fixed head conformations. On the contrary, their hydrophobic tails adopt different configurations to make contacts with hydrophobic region. The oxadiazole-ring-related hydrogen bond interactions well elucidate the structural features governing the different binding behavior of these agonists against PPARalpha and PPARgamma. Based on these active conformations, highly predictive comparative molecular similarity indices analysis (CoMSIA) models were derived, which not only is consistent with the experimental results but also could be mapped back to the receptor topology and the ligand-receptor interaction models. The simulation results reveal the structure-activity relationship of these compounds at the molecular level and provide new insights for the design of novel potent PPARalpha and PPARgamma dual agonists.
Authors:
Feng Cheng; Jianhua Shen; Xiaoying Xu; Xiaomin Luo; Kaixian Chen; Xu Shen; Hualiang Jiang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Protein and peptide letters     Volume:  16     ISSN:  0929-8665     ISO Abbreviation:  Protein Pept. Lett.     Publication Date:  2009  
Date Detail:
Created Date:  2009-02-09     Completed Date:  2009-08-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9441434     Medline TA:  Protein Pept Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  150-62     Citation Subset:  IM    
Affiliation:
Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Computer Simulation
Hydrophobicity
Ligands
Models, Chemical
Models, Molecular
Molecular Sequence Data
Oxadiazoles / chemistry*
PPAR alpha / chemistry*
PPAR gamma / chemistry*
Propionic Acids / chemistry*
Protein Binding
Quantitative Structure-Activity Relationship
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Ligands; 0/Oxadiazoles; 0/PPAR alpha; 0/PPAR gamma; 0/Propionic Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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