| Insight into the Fundamental Interactions between LEDGF Binding Site Inhibitors and Integrase Combining Docking and Molecular Dynamics Simulations. | |
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MedLine Citation:
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PMID: 23194297 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Laura De Luca; Francesca Morreale; Alba Chimirri |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-29 |
Journal Detail:
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Title: Journal of chemical information and modeling Volume: - ISSN: 1549-960X ISO Abbreviation: J Chem Inf Model Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101230060 Medline TA: J Chem Inf Model Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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