Simulation of the interactions between Tröger bases and DNA

Ricci, Clarisse Gravina; Netz, Paulo Augusto

doi:10.1590/s0103-50532012000700019

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…Minor-groove binding agents such as TBs and their derivatives usually have structures that allowed them to adopt a crescent shape that fits into the minor groove. , Within the minor groove, close contacts are formed in the deep, narrowed space between the two complementary strands of a duplex DNA. These minor-groove binder complexes involve hydrogen bonds (HBsa), van der Waals contacts, and/or ionic interactions for stabilization .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA Duplex Winding in Cancer Cells

Tripathi

Misra

Ostadhossein

et al. 2018

ACS Appl. Mater. Interfaces

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Targeting the DNA of tumor cells with small molecules may offer effective clinical strategies for transcriptional inhibition. We unveil synthesis and characterization of ∼20 nm chiral carbon nanoparticles for enantiospecific recognition of DNA. Our approach inculcates chirality in carbon nanoparticles by controlled tethering of minor groove binders, i.e., Tröger’s base (TB). The chiral particles positively enriched the cellular nucleus in MCF-7 breast cancer cells, irrespective of the TB asymmetry tethered on the particle surface, but negatively induced chiral carbon nanoparticles exhibited improved efficiency at inhibiting cell growth. Further studies indicated that these chiral particles act as nanotweezers to perturb the genomic DNA and induce apoptosis cascade in cancer cells.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA Duplex Winding in Cancer Cells

Tripathi

Misra

Ostadhossein

et al. 2018

ACS Appl. Mater. Interfaces

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“…It is clear from Figure S3 d–h that the oligomer is beginning to fray at the 5′ end as early as 30 ns. The few simulations that have been performed previously on DNA with a single minor groove binder have been shorter than this simulation: 20 ns for a Tröger base bound to DNA (Ricci and Netz, ) and 5 ns for a series of 1:1 binders in the minor groove (Srivastava et al ., ). As such, those simulations would not have observed this fraying.…”

Section: Resultsmentioning

confidence: 99%

“…While there does not appear to be a high degree of curvature in the oligomer, the flexibility of the DNA must be examined separately. To characterize the flexibility of the DNA backbone in the complex, the torsional parameters α (O3′‐P‐O5′‐C5′), γ (O5′‐C5′‐C4′‐C3′), ε (C4′‐C3′‐O3′‐P), and ζ (C3′‐O3′‐P‐O5′) are reported (Ricci and Netz, ).…”

Section: Resultsmentioning

confidence: 99%

“…While much experimental work has been performed on nucleic acids, molecular dynamics (MD) simulations of DNA has become a strong area of research more recently (Beveridge et al, 2004;Perez et al, 2007a;Perez et al, 2012;Lavery et al, 2010;Ricci et al, 2010;Ricci and Netz, 2012;Zgarbova et al, 2013) particularly with the large number of groups involved in the ABC initiative . While there have been reports from groups who are working at the intersection of these two important fields of research: the search for a highly selective, strongly binding minor groove binder and the characterization of DNA by computational techniques, they have either focused solely on docking studies (Collar et al, 2010) or on molecules that bind in a 1:1 fashion (Srivastava et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic hydrogen bonding and DNA flexibility in minor groove binders: molecular dynamics simulation of the polyamide f‐ImPyIm bound to the Mlu1 (MCB) sequence 5′‐ACGCGT‐3′ in 2:1 motif

Bruce

Ferrara

Manka

et al. 2015

J of Molecular Recognition

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Molecular dynamics simulations of the DNA 10-mer 5'-CCACGCGTGG-3' alone and complexed with the formamido-imidazole-pyrrole-imidazole (f-ImPyIm) polyamide minor groove binder in a 2:1 fashion were conducted for 50 ns using the pbsc0 parameters within the AMBER 12 software package. The change in DNA structure upon binding of f-ImPyIm was evaluated via minor groove width and depth, base pair parameters of Slide, Twist, Roll, Stretch, Stagger, Opening, Propeller, and x-displacement, dihedral angle distributions of ζ, ε, α, and γ determined using the Curves+ software program, and hydrogen bond formation. The dynamic hydrogen bonding between the f-ImPyIm and its cognate DNA sequence was compared to the static image used to predict sequence recognition by polyamide minor groove binders. Many of the predicted hydrogen bonds were present in less than 50% of the simulation; however, persistent hydrogen bonds between G5/15 and the formamido group of f-ImPyIm were observed. It was determined that the DNA is wider in the Complex than without the polyamide binder; however, there is flexibility in this particular sequence, even in the presence of the f-ImPyIm as evidenced by the range of minor groove widths the DNA exhibits and the dynamics of the hydrogen bonding that binds the two f-ImPyIm ions to the minor groove. The Complex consisting of the DNA and the 2 f-ImPyIm binders shows slight fraying of the 5' end of the 10-mer at the end of the simulation, but the portion of the oligomer responsible for recognition and binding is stable throughout the simulation. Several structural changes in the Complex indicate that minor groove binders may have a more active role in inhibiting transcription than just preventing binding of important transcription factors.

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“…As the intercalation involves both the opening of an intercalation gap and also the local unwinding of the double helix, the effect of the ligand could be clearly followed in the Rise/Twist conformational space 47. Figure 6, combining the information of Rise and Twist parameters, shows as scattered points in a Rise/Twist conformational space the distribution of the base pair step AA values for LIG1 and LIG1′ (both for intercalation and minor groove binding complex).…”

Section: Resultsmentioning

confidence: 99%

Benzothiadiazoles as DNA intercalators: Docking and simulation

Netz

2012

Int J of Quantum Chemistry

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Some organic dyes, derivatives of the 4-(arylethynyl)-7-(4-methoxyphenyl)-2,1,3-benzothiadiazoles (BTDs) bind strongly to double stranded DNA, exhibiting a strong increase in the fluorescence intensity. Due to this property, they were proposed as very sensitive probes for DNA detection and quantification.The details of the interaction mechanism, however, are unknown. In this work, we use docking and molecular dynamics simulations to study the interactions of these BTDs with DNA. We used a docking protocol where the receptor is a modified canonical oligonucleotide, with a gap, to sample intercalation and minor groove binding modes. Starting from several independent but energetically favorable docking poses, molecular dynamics simulations were carried out, investigating the ligand-DNA interactions and the time evolution of the DNA structure. We observed, in agreement with experimental results, that the presence of the ethynyl spacer in the ligand stabilizes the intercalation binding mode, yielding strong interactions with DNA and large residence times.

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Simulation of the interactions between Tröger bases and DNA

Cited by 9 publications

References 44 publications

Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA Duplex Winding in Cancer Cells

Synthesis of Chiral Carbo-Nanotweezers for Enantiospecific Recognition and DNA Duplex Winding in Cancer Cells

Dynamic hydrogen bonding and DNA flexibility in minor groove binders: molecular dynamics simulation of the polyamide f‐ImPyIm bound to the Mlu1 (MCB) sequence 5′‐ACGCGT‐3′ in 2:1 motif

Benzothiadiazoles as DNA intercalators: Docking and simulation

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