2D-IR Spectroscopy Shows that Optimized DNA Minor Groove Binding of Hoechst33258 Follows an Induced Fit Model

Ramakers, Lennart A. I.; Hithell, Gordon; May, John; Greetham, Gregory M.; Donaldson, Paul M.; Towrie, Michael; Parker, Anthony W.; Burley, Glenn A.; Hunt, Neil T.

doi:10.1021/acs.jpcb.7b00345

Cited by 28 publications

(57 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the diagonal peak at 1702 cm −1 of H-DNA is clearly stronger than that of native DNA, appearing with a cross peak ω 1 / ω 3 = 1670/1702 cm −1 , arising from the thymine (T) C 2 =O carbonyl. These changes are similar to those observed by Hunt and co-workers for H binding to duplex 5′-GCAAATTTGC-3′ 26 . Such behavior has also been observed in the FTIR spectra, a shoulder peak appears at 1702 cm −1 upon ligand binding (highlighted with an arrow in Fig.…”

Section: Resultssupporting

confidence: 90%

“…The prominent mobility of H helps in forming and stabilizing the critical nucleus, which is essential in the hybridization of canonical DNA. Conformational changes of DNA and displacement of spine of hydration, are considered as the last step in forming a stable H-DNA complex that are sequence-dependent due to the superior accommodation of H 26 .…”

Section: Dissociation Of H-dna Observed By T-jump Irmentioning

confidence: 99%

“…The association of H with DNA duplex (dsDNA), is entropy-driven and proceeds with a large and unfavorable change in enthalpy 19 . The hydration entropy change, resulting from the release of water in the DNA minor groove to the bulk, is much larger than the change in configurational entropy [20][21][22][23][24][25][26] . The displacement of hydration water by H highly improves the stability of dsDNA structure with subtle conformational distortions [27][28][29] .…”

mentioning

confidence: 99%

See 2 more Smart Citations

DNA minor-groove binder Hoechst 33258 destabilizes base-pairing adjacent to its binding site

et al. 2020

View full text Add to dashboard Cite

Understanding the dynamic interactions of ligands to DNA is important in DNA-based nanotechnologies. By structurally tracking the dissociation of Hoechst 33258-bound DNA (d(CGCAAATTTGCG)2) complex (H-DNA) with T-jump 2D-IR spectroscopy, the ligand is found to strongly disturb the stability of the three C:G base pairs adjacent to A:T the binding site, with the broken base pairs being more than triple at 100 ns. The strong stabilization effect of the ligand on DNA duplex makes this observation quite striking, which dramatically increases the melting temperature and dissociation time. MD simulations demonstrate an important role of hydration water and counter cations in maintaining the separation of terminal base pairs. The hydrogen bonds between the ligand and thymine carbonyls are crucial in stabilizing H-DNA, whose breaking signal appearing prior to the complete dissociation. Thermodynamic analysis informs us that H-DNA association is a concerted process, where H cooperates with DNA single strands in forming H-DNA.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Dissociation Of H-dna Observed By T-jump Irmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

DNA minor-groove binder Hoechst 33258 destabilizes base-pairing adjacent to its binding site

et al. 2020

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5][6] The couplings of these base modes makes them sensitive reporters of DNA structure and they have been used to determine the spectroscopic effects of base stacking [7,8] as well as the sequence-dependent impact of ligand binding on the structure of the double helix. [9] Transient 2D-IR spectroscopy methods have observed the melting of dsDNA sequences. [10] The interaction of DNA with the aqueous solvent has also been studied with 2D-IR spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

Effect of oligomer length on vibrational coupling and energy relaxation in double-stranded DNA

Hithell¹,

Donaldson

Greetham

et al. 2018

Chemical Physics

Self Cite

View full text Add to dashboard Cite

The effect of oligomer length on the vibrational mode coupling and energy relaxation mechanisms of AT-rich DNA oligomers in double- and single-stranded conformations has been investigated using two-dimensional infrared spectroscopy. Vibrational coupling of modes of the DNA bases to the symmetric stretching vibration of the backb one phosphate group was observed for oligomers long enough to form duplex-DNA structures. The coupling was lost upon melting of the duplex. No significant effect of oligomer length or DNA secondary structure was found on either the timescale for vibrational relaxation of the base modes or the mechanism, which was consistent with a cascade process from base modes to intermediate modes, some of which are located on the deoxyribose group, and subsequently to the phosphate backbone. The study shows that vibrational coupling between base and backbone requires formation of the double-helix structure while vibrational energy management is an inherent property of the nucleotide

show abstract

“…In the case of PF-poly(dA)·poly(dT) complex, the conformational changes are not so large but they are still important for tighter PF-DNA binding: the change of the propeller twist and the increased opening in the PF binding site optimize specific hydrogen bonds between the PF and poly(dA)·poly(dT). Recently Ramakers and coworkers reported that the binding of Hoechst33258 to the A-tract DNA induces subtle conformational changes in the DNA structure, which maximize favorable ligand-DNA interactions [57]. The results of our study and that of Ramakers indicate that the model of rigid DNA-target is not a good choice even for small minor groove binders.…”

Section: Discussionmentioning

confidence: 53%

Ligand-induced DNA conformational changes in proflavine minor groove-bound complexes studied by molecular dynamics simulation

2019

Biophysical Bulletin

View full text Add to dashboard Cite

Background: Minor groove binding is a rate-limiting step in proflavine-DNA intercalation reaction. This step is believed also to be responsible for the sequence-dependent kinetics of proflavine binding to DNA. At the same time, most studies are focused on the final stage of the reaction – the intercalation complex, and there is a lack of data concerning the structure and stability of proflavine-DNA minor groove-bound complexes. Objectives: The objective of this study was to investigate the stability of proflavine minor groove-bound complexes with DNA oligonucleotides of different sequence by molecular dynamics simulation and to analyze the DNA conformational changes caused by the proflavine binding. Materials and methods: The molecular dynamics simulations of proflavine minor groove-bound complexes with poly(dA)·poly(dT) and poly(dCG)·poly(dCG) oligonucleotides of 30 bp length were done in program package AMBER12 with explicit water (SPC/E) and ions (NaCl 0.15 M) using force fields FF14SB for DNA and GAFF for ligand. The starting configurations of complexes were obtained by docking method in AutoDock 3.05. After multi-stage equilibration protocol, each system was simulated at T=300 K and p=1 bar for a 50 ns production phase. Then trajectories were post-processed in AMBERTools17 and VMD-1.9.3 packages. Results: Our simulations confirm that proflavine-DNA minor groove-bound complexes are stable in the 50 ns time range but there are some structural rearrangements in them with respect to the initial structures. The narrowing of the DNA minor groove is observed in the proflavine binding site. In proflavine-poly(dCG)·poly(dCG) complex it is more pronounced and is accompanied by the BI/BII transitions in DNA and the reorientation of ligand. In proflavine-poly(dA)·poly(dT) complex the specific intermolecular hydrogen bonds are formed, which are optimized by the changes in opening and propeller twisting of involved AT-base pairs. Complexes are stabilized by the van der Waals and hydrophobic interactions, which are more favorable in the proflavine-poly(dA)·poly(dT) complex. Conclusions: Our results show that the binding of proflavine to a minor groove of DNA induces the conformational changes in the DNA that are important for the resulting complex stability.

show abstract

2D-IR Spectroscopy Shows that Optimized DNA Minor Groove Binding of Hoechst33258 Follows an Induced Fit Model

Cited by 28 publications

References 47 publications

DNA minor-groove binder Hoechst 33258 destabilizes base-pairing adjacent to its binding site

DNA minor-groove binder Hoechst 33258 destabilizes base-pairing adjacent to its binding site

Effect of oligomer length on vibrational coupling and energy relaxation in double-stranded DNA

Ligand-induced DNA conformational changes in proflavine minor groove-bound complexes studied by molecular dynamics simulation

Contact Info

Product

Resources

About