Document Detail

Insight into the Fundamental Interactions between LEDGF Binding Site Inhibitors and Integrase Combining Docking and Molecular Dynamics Simulations.
MedLine Citation:
PMID:  23194297     Owner:  NLM     Status:  Publisher    
In recent years HIV-1 integrase (IN), has emerged as an attractive target for novel anti-AIDS agents. In particular nonactive-site-binding IN inhibitors would display synergy with current strand-transfer-specific IN inhibitors and other antiretroviral drugs in clinical use. An effective allosteric inhibitory approach would be the disruption of protein-protein interaction (PPI) between IN and cellular cofactors, such as LEDGF/p75. To date, several small molecules have been reported to be inhibitors of the PPI between IN and LEDGF/p75. In this study, we investigated the most relevant interactions between five selected PPI inhibitors and IN comparing them to the naturally occurring IN-LEDGF/p75 complex. We calculated the binding free energies by using the method of molecular mechanics-generalized born surface area (MM-GBSA). Total energy was decomposed on per-residue contribution, and hydrogen bond occupancies were monitored throughout the simulations. Considering all these results we obtained a good correlation with experimental activity and useful insights for the development of new inhibitors.
Laura De Luca; Francesca Morreale; Alba Chimirri
Related Documents :
24785777 - Homooligomerization is needed for stability: a molecular modelling and solution study o...
23047027 - Hydrolysis of low concentrations of the acetylthiocholine analogs acetyl(homo)thiocholi...
24505347 - A novel angiotensin i-converting enzyme mutation (s333w) impairs n-domain enzymatic cle...
24180557 - Hydroxyindole carboxylic acid based inhibitors for receptor-type protein tyrosine prote...
17878167 - Production and characterization of rna aptamers specific for amyloid fibril epitopes.
11278037 - Immobilization of sugar-non-specific nucleases by utilizing the streptavidin--biotin in...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-29
Journal Detail:
Title:  Journal of chemical information and modeling     Volume:  -     ISSN:  1549-960X     ISO Abbreviation:  J Chem Inf Model     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101230060     Medline TA:  J Chem Inf Model     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Characterization of transferrin receptor-mediated endocytosis and cellular iron delivery of recombin...
Next Document:  A periconceptional energy-rich dietary pattern is associated with early fetal growth: the Generation...