Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.

HIV-1 integrase (IN) is an important target in the development of drugs against the AIDS virus. Drug design based on the structure of IN was markedly hampered due to the lack of three-dimensional structure information of HIV-1 IN-viral DNA complex. The prototype foamy virus (PFV) IN has a highly fun...

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Autores principales:	Jianping Hu, Ming Liu, Dianyong Tang, Shan Chang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71eec6b5bbf44187b6634a46489104b8
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spelling	oai:doaj.org-article:71eec6b5bbf44187b6634a46489104b82021-11-18T08:00:00ZSubstrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.1932-620310.1371/journal.pone.0054929https://doaj.org/article/71eec6b5bbf44187b6634a46489104b82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23365687/?tool=EBIhttps://doaj.org/toc/1932-6203HIV-1 integrase (IN) is an important target in the development of drugs against the AIDS virus. Drug design based on the structure of IN was markedly hampered due to the lack of three-dimensional structure information of HIV-1 IN-viral DNA complex. The prototype foamy virus (PFV) IN has a highly functional and structural homology with HIV-1 IN. Recently, the X-ray crystal complex structure of PFV IN with its cognate viral DNA has been obtained. In this study, both Gaussian network model (GNM) and anisotropy network model (ANM) have been applied to comparatively investigate the motion modes of PFV DNA-free and DNA-bound IN. The results show that the motion mode of PFV IN has only a slight change after binding with DNA. The motion of this enzyme is in favor of association with DNA, and the binding ability is determined by its intrinsic structural topology. Molecular docking experiments were performed to gain the binding modes of a series of diketo acid (DKA) inhibitors with PFV IN obtained from ANM, from which the dependability of PFV IN-DNA used in the drug screen for strand transfer (ST) inhibitors was confirmed. It is also found that the functional groups of keto-enol, bis-diketo, tetrazole and azido play a key role in aiding the recognition of viral DNA, and thus finally increase the inhibition capability for the corresponding DKA inhibitor. Our study provides some theoretical information and helps to design anti-AIDS drug based on the structure of IN.Jianping HuMing LiuDianyong TangShan ChangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54929 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jianping Hu Ming Liu Dianyong Tang Shan Chang Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
description	HIV-1 integrase (IN) is an important target in the development of drugs against the AIDS virus. Drug design based on the structure of IN was markedly hampered due to the lack of three-dimensional structure information of HIV-1 IN-viral DNA complex. The prototype foamy virus (PFV) IN has a highly functional and structural homology with HIV-1 IN. Recently, the X-ray crystal complex structure of PFV IN with its cognate viral DNA has been obtained. In this study, both Gaussian network model (GNM) and anisotropy network model (ANM) have been applied to comparatively investigate the motion modes of PFV DNA-free and DNA-bound IN. The results show that the motion mode of PFV IN has only a slight change after binding with DNA. The motion of this enzyme is in favor of association with DNA, and the binding ability is determined by its intrinsic structural topology. Molecular docking experiments were performed to gain the binding modes of a series of diketo acid (DKA) inhibitors with PFV IN obtained from ANM, from which the dependability of PFV IN-DNA used in the drug screen for strand transfer (ST) inhibitors was confirmed. It is also found that the functional groups of keto-enol, bis-diketo, tetrazole and azido play a key role in aiding the recognition of viral DNA, and thus finally increase the inhibition capability for the corresponding DKA inhibitor. Our study provides some theoretical information and helps to design anti-AIDS drug based on the structure of IN.
format	article
author	Jianping Hu Ming Liu Dianyong Tang Shan Chang
author_facet	Jianping Hu Ming Liu Dianyong Tang Shan Chang
author_sort	Jianping Hu
title	Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
title_short	Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
title_full	Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
title_fullStr	Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
title_full_unstemmed	Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.
title_sort	substrate recognition and motion mode analyses of pfv integrase in complex with viral dna via coarse-grained models.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/71eec6b5bbf44187b6634a46489104b8
work_keys_str_mv	AT jianpinghu substraterecognitionandmotionmodeanalysesofpfvintegraseincomplexwithviraldnaviacoarsegrainedmodels AT mingliu substraterecognitionandmotionmodeanalysesofpfvintegraseincomplexwithviraldnaviacoarsegrainedmodels AT dianyongtang substraterecognitionandmotionmodeanalysesofpfvintegraseincomplexwithviraldnaviacoarsegrainedmodels AT shanchang substraterecognitionandmotionmodeanalysesofpfvintegraseincomplexwithviraldnaviacoarsegrainedmodels
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Substrate recognition and motion mode analyses of PFV integrase in complex with viral DNA via coarse-grained models.

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