Document Detail

Molecular dynamics and free energy studies of chirality specificity effects on aminobenzo[a]quinolizine inhibitors binding to DPP-IV.
MedLine Citation:
PMID:  23151852     Owner:  NLM     Status:  Publisher    
The aminobenzo[a]quinolizines were investigated as a novel class of DPP-IV inhibitors. The stereochemistry of this class plays an important role in the bioactivity. In this study, the mechanisms of how different configuration of three chiral centers of this class influences the binding affinity were investigated by molecular dynamics simulations, free energy decomposition analysis. The S configuration for chiral center 3* is decisive for isomers to maintain high bioactivity; the chirality effect of chiral center 2* on the binding affinity is largely dependent, while the S configuration for chiral center 2* is preferable to R configuration for the bioactivity gain; the effect of chiral center 11b* on the binding affinity is insignificant. The chirality specificity for three chiral centers is responsible for distinction of two van der Waals contacts with Tyr547 and Phe357, and of H-bonding interactions with Arg125 and Glu206. Particularly, the Arg125 to act as a bridge in the H-bonding network contributes to stable H-bonding interactions of isomer in DPP-IV active site.
Cui Wei; Liang Desheng; Gao Jian; Luo Fang; Geng Lingling; Ji Mingjuan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-15
Journal Detail:
Title:  Journal of molecular modeling     Volume:  -     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
College of Chemistry and Chemical Engineering, Graduate University of the Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
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