Abstract
In this paper we applied the “macromolecular docking” procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift assays (EMSA) and surface plasmon resonance (SPR) based biospecific interaction analysis (BIA) using an optical biosensor. Finally the specific interactions between NF-κB and RNA have been calculated utilizing the AMBER-MM and FMO calculations. The results obtained clearly indicate that (a) NF-kB p50 transcription factor can bind TAR-RNA; (b) this binding efficiency is lower than that displayed by NF-kB factor in respect to DNA sequences; (c) other structured RNAs used as controls do not bind to NF-kB; (d) TAR-RNA is capable to bind pre-formed NF-kB/DNA complexes. Despite the fact that our data do not indicate whether NF-kB/TAR-RNA complexes play a role in the early steps of HIV-1 transcriptional activation, the results presented strongly indicate that interactions between transcription factors recruited at the level of HIV-1 LTR might interact with the TAR-RNA and deserve further studies aimed to determine its role in the HIV-1 life cycle.
Keywords: HIV-1; AIDS; TAR-RNA; NF-kB; Molecular Modeling; Docking, transcription factors, molecular mechanics, Fourier transformation, Protein–protein interactions, fragment molecular orbital
Current Topics in Medicinal Chemistry
Title:Structure-Based Analysis of the Molecular Recognitions Between HIV-1 TAR-RNA and Transcription Factor Nuclear Factor-kappaB (NFkB)
Volume: 12 Issue: 8
Author(s): Mahmud Tareq Hassan Khan, Carlo Mischiati, Arjumand Ather, Tatsuya Ohyama, Kenichi Dedachi, Monica Borgatti, Noriyuki Kurita and Roberto Gambari
Affiliation:
Keywords: HIV-1; AIDS; TAR-RNA; NF-kB; Molecular Modeling; Docking, transcription factors, molecular mechanics, Fourier transformation, Protein–protein interactions, fragment molecular orbital
Abstract: In this paper we applied the “macromolecular docking” procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift assays (EMSA) and surface plasmon resonance (SPR) based biospecific interaction analysis (BIA) using an optical biosensor. Finally the specific interactions between NF-κB and RNA have been calculated utilizing the AMBER-MM and FMO calculations. The results obtained clearly indicate that (a) NF-kB p50 transcription factor can bind TAR-RNA; (b) this binding efficiency is lower than that displayed by NF-kB factor in respect to DNA sequences; (c) other structured RNAs used as controls do not bind to NF-kB; (d) TAR-RNA is capable to bind pre-formed NF-kB/DNA complexes. Despite the fact that our data do not indicate whether NF-kB/TAR-RNA complexes play a role in the early steps of HIV-1 transcriptional activation, the results presented strongly indicate that interactions between transcription factors recruited at the level of HIV-1 LTR might interact with the TAR-RNA and deserve further studies aimed to determine its role in the HIV-1 life cycle.
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Tareq Hassan Khan Mahmud, Mischiati Carlo, Ather Arjumand, Ohyama Tatsuya, Dedachi Kenichi, Borgatti Monica, Kurita Noriyuki and Gambari Roberto, Structure-Based Analysis of the Molecular Recognitions Between HIV-1 TAR-RNA and Transcription Factor Nuclear Factor-kappaB (NFkB), Current Topics in Medicinal Chemistry 2012; 12 (8) . https://dx.doi.org/10.2174/156802612800166800
DOI https://dx.doi.org/10.2174/156802612800166800 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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