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231224s2012 xx |||||o 00| ||eng c |
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|a 10.1002/jcc.22887
|2 doi
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|a pubmed24n0712.xml
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|a (DE-627)NLM213616386
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|a (NLM)22144113
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Xue, Weiwei
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Molecular mechanism of HIV-1 integrase-vDNA interactions and strand transfer inhibitor action
|b a molecular modeling perspective
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|c 2012
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 07.05.2012
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|a Date Revised 01.12.2018
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2011 Wiley Periodicals, Inc.
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|a Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme for splicing a viral DNA (vDNA) replica of its genome into host cell chromosomal DNA (hDNA) and has been recently recognized as a promising therapeutic target for developing anti-AIDS agents. The interaction between HIV-1 IN and vDNA plays an important role in the integration process of the virus. However, a detailed understanding about the mechanism of this interactions as well as the action of the anti-HIV drug raltegravir (RAL, approved by FDA in 2007) targeting HIV-1 IN in the inhibition of the vDNA strand transfer is still absent. In the present work, a molecular modeling study by combining homology modeling, molecular dynamics (MD) simulations with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and molecular mechanics Generalized-Born surface area (MM-GBSA) calculations was performed to investigate the molecular mechanism of HIV-1 IN-vDNA interactions and the inhibition action of vDNA strand transfer inhibitor (INSTI) RAL. The structural analysis showed that RAL did not influence the interaction between vDNA and HIV-1 IN, but rather targeted a special conformation of HIV-1 IN to compete with host DNA and block the function of HIV-1 IN by forcing the 3'-OH of the terminal A17 nucleotide away from the three catalytic residues (Asp64, Asp116, and Glu152) and two Mg(2+) ions. Thus, the obtained results could be helpful for understanding of the integration process of the HIV-1 virus and provide some new clues for the rational design and discovery of potential compounds that would specifically block HIV-1 virus replication
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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| 650 |
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|a DNA, Viral
|2 NLM
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| 650 |
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7 |
|a HIV Integrase
|2 NLM
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| 650 |
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7 |
|a EC 2.7.7.-
|2 NLM
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| 650 |
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|a p31 integrase protein, Human immunodeficiency virus 1
|2 NLM
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| 650 |
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|a YY6481J2FF
|2 NLM
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| 700 |
1 |
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|a Liu, Huanxiang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yao, Xiaojun
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 33(2012), 5 vom: 15. Feb., Seite 527-36
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
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| 773 |
1 |
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|g volume:33
|g year:2012
|g number:5
|g day:15
|g month:02
|g pages:527-36
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|u http://dx.doi.org/10.1002/jcc.22887
|3 Volltext
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