Interaction identification of Zif268 and TATA<sub>ZF</sub> proteins with GC‐/AT‐rich DNA sequence: A theoretical study

Yang, Bo; Zhu, Yanyan; Wang, Yan; Chen, Guangju

doi:10.1002/jcc.21630

Cited by 34 publications

(25 citation statements)

References 74 publications

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“…A hydrophobic contact is defined as a distance between carbon atoms shorter than 4.5 Å [38]. All hydrophobic contacts between nucleic acid residues and protein residues are listed.…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Zhou¹,

Pan

et al. 2013

Theor Biol Med Model

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BackgroundToll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via the adaptor protein MyD88. However, the specific sequence and structural requirements of the CpG DNA for the recognition of and binding to TLR9 are unknown. Moreover, the 3D structures of TLR9 and the TLR9-ODN complex have not been determined. In this study, we propose a reliable model of the interaction of the TLR9 ECD with CpG ODN using bioinformatics tools.ResultsThe three-dimensional structures of two TLR9 ECD-CpG ODN complexes were constructed using a homology modelling and docking strategy. Based on the models of these complexes, the TLR9 ECD-CpG ODN interaction patterns were calculated. The results showed that the interface between the human TLR9 and the CpG ODN molecule is geometrically complementary. The computed molecular interactions indicated that LRR11 is the main region of TLR9 that binds to CpG ODN and that five positively charged residues within LRR11 are involved in the binding of the TLR9 ECD to the CpG ODN. Observations in the close-up view of these interactions indicated that these five positively charged residues contribute differently to the binding region within the TLR9 ECD-CpG ODN complex. 337Arg and 338Lys reside in the binding sites of ODN, forming hydrogen bonds and direct contacts with the CpG ODN, whereas 347Lys, 348Arg, and 353His do not directly contact the CpG ODN. These results are in agreement with previously reported experimental data.ConclusionIn this study, we present two structural models for the human and mouse TLR9 ECD in a complex with CpG ODN. Some features predicted by this model are consistent with previously reported experimental data. This complex model may lead to a better understanding of the function of TLR9 and its interaction with CpG ODN and will improve our understanding of TLR9-ligand interaction in general.

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“…A hydrophobic contact is defined as a distance between carbon atoms shorter than 4.5 Å [38]. All hydrophobic contacts between nucleic acid residues and protein residues are listed.…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Zhou¹,

Pan

et al. 2013

Theor Biol Med Model

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“…The force field parameters and RESP charges of the zinc centers of the GRDBD dimer were referenced from the previous work [33].…”

Section: Methodsmentioning

confidence: 99%

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Wang

et al. 2012

PLoS ONE

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BackgroundIt has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect the DNA dependent binding by interfering with the protein-DNA interface. However, how such small molecules affect the transcription factor-DNA interfaces and gene regulatory pathways through DNA structure distortion is not fully understood so far.Methodology/Principal FindingsIn the present work, we have constructed some models, especially the ternary model of polyamides+DNA+GR DNA-binding domain (GRDBD) dimer, and carried out molecular dynamics simulations and free energy calculations for them to address how polyamide molecules disrupt the GRDBD and DNA interface when polyamide and protein bind at the same sites on opposite grooves of DNA.Conclusions/SignificanceWe found that the cyclic polyamide binding in minor groove of DNA can induce a large structural perturbation of DNA, i.e. a >4 Å widening of the DNA minor groove and a compression of the major groove by more than 4 Å as compared with the DNA molecule in the GRDBD dimer+DNA complex. Further investigations for the ternary system of polyamides+DNA+GRDBD dimer and the binary system of allosteric DNA+GRDBD dimer revealed that the compression of DNA major groove surface causes GRDBD to move away from the DNA major groove with the initial average distance of ∼4 Å to the final average distance of ∼10 Å during 40 ns simulation course. Therefore, this study straightforward explores how small molecule targeting specific sites in the DNA minor groove disrupts the transcription factor-DNA interface in DNA major groove, and consequently modulates gene expression.

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“…MM_PBSA method is a very useful tool for obtaining relative binding free energies of receptor and ligand [48]. In the study of the variety of nucleic acid systems, it has proven useful to investigate drug molecules binding to DNA [49,50].…”

Section: Mm_pbsa Approachmentioning

confidence: 99%

“…where G adduct , G DNA and G nuclease are the free energies of adduct, DNA and nuclease molecule, respectively [48]. The free energy (G) of each state is estimated from molecular mechanical energy E MM , solvation free energy G solv and solute entropy S, respectively.…”

Section: Mm_pbsa Approachmentioning

confidence: 99%

Theoretical study on binding models of copper nucleases containing pyridyl groups to DNA

Zhang

Tang

et al. 2015

Theor Chem Acc

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Interaction identification of Zif268 and TATA_ZF proteins with GC‐/AT‐rich DNA sequence: A theoretical study

Cited by 34 publications

References 74 publications

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Theoretical study on binding models of copper nucleases containing pyridyl groups to DNA

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Interaction identification of Zif268 and TATAZF proteins with GC‐/AT‐rich DNA sequence: A theoretical study

Cited by 34 publications

References 74 publications

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Theoretical study on binding models of copper nucleases containing pyridyl groups to DNA

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Interaction identification of Zif268 and TATA_ZF proteins with GC‐/AT‐rich DNA sequence: A theoretical study