Mechanistic Insights into the Ligand-Induced Unfolding of an RNA G-Quadruplex

Haldar, Susanta; Zhang, Yashu; Xia, Ying; Islam, Barira; Liu, Sisi; Gervasio, Francesco Luigi; Mulholland, Adrian J.; Waller, Zoë A. E.; Wei, Dengguo; Haider, Shozeb

doi:10.1021/jacs.1c11248

Cited by 44 publications

(33 citation statements)

References 108 publications

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“…The dissociation rates however are relatively higher, which eventually give rise to the lower binding affinity of Hoechst(s) to the G-tetrads (see Figure ). Nevertheless, unbiased and biased MD simulations on these ligand/quadruplex systems may possibly capture the actual binding modes of these ligands and also the free energy landscape of the ligand/quadruplex interactions. , …”

Section: Resultsmentioning

confidence: 99%

G-Tetrad-Selective Ligand Binding Kinetics in G-Quadruplex DNA Probed with Fluorescence Correlation Spectroscopy

Clovis

Sen

2022

J. Phys. Chem. B

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Probing the kinetics of ligand binding to biomolecules is of paramount interest in biology and pharmacology. Measurements of such kinetic processes provide information on the rate-determining steps that control the binding affinity of ligands to biomolecules, thereby predicting the mechanism of the molecular interaction. In this context, ligand binding to G-quadruplex DNA (GqDNA) structures has attracted tremendous attention primarily because of their use in possible anticancer therapy. Although a large number of G-quadruplex-specific ligands have been proposed, probing the kinetics of G-tetrad-selective binding of (multiple) ligands within a G-quadruplex DNA (GqDNA) structure remains challenging. Most of the earlier studies focused on the thermodynamics of ligand binding; however, the kinetics of ligand association and dissociation with GqDNA, particularly binding of multiple ligands within a GqDNA structure, have not been explored. Here, we propose a simple fluorescence correlation spectroscopy-based method that measures the G-tetrad-selective association and dissociation rates of ligands within a GqDNA structure by correlating the fluorescence fluctuations of a site-specific (5′ or 3′ end-labeled) fluorophore (Cy3) in GqDNA due to quenching of Cy3 fluorescence, induced by the ligand binding to the G-tetrads. We show that well-known GqDNA ligands, BRACO19, TMPyP4, Hoechst 33258, and Hoechst 33342, have G-tetrad-selective association and dissociation rates, which suggest site-dependent variation of free energy barriers for binding/unbinding of the ligands with GqDNA. We also show that the measured kinetic rates depend not only on the G-tetrad site (5′ vs 3′ end) but also on the ligand and GqDNA structures.

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Section: Resultsmentioning

confidence: 99%

G-Tetrad-Selective Ligand Binding Kinetics in G-Quadruplex DNA Probed with Fluorescence Correlation Spectroscopy

Clovis

Sen

2022

J. Phys. Chem. B

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“…Interestingly, TMPyP4 exerted opposite effect on PQS structures, stabilization, and destabilization. TMPyP4 increased G4 stability through stacking its aromatic core on the upper or lower G4 tetrad ( 38 ), whereas TMPyP4 induced G4 unfolding through two conformation states composed of groove-bound and top-face-bound ( 39 ). The nature of binding mode of TMPyP4 to G4 remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Characterization of G-Quadruplexes in Enterovirus A71 Genome and Their Interaction with G-Quadruplex Ligands

Zhang

2022

Microbiol Spectr

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“…Although it is possible to achieve the value that is needed for the parameter, this technique is inefficient. The idea came from Susanta Haldar and a few other people [ 33 ].…”

Section: Literature Surveymentioning

confidence: 99%

“…This approach results in a 7.4 percent reduction in power consumption for the transmission of each bit. An embedded transition inversion (ETI) coding was determined by the phase difference between the data clock and the driving clock [ 33 ].…”

Section: Proposed Workmentioning

confidence: 99%

Cryptography-Based Medical Signal Securing Using Improved Variation Mode Decomposition with Machine Learning Techniques

Shukla

Akanbi

Asakipaam

et al. 2022

Computational Intelligence and Neuroscience

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There is no question about the value that digital signal processing brings to the area of biomedical research. DSP processors are used to sample and process the analog inputs that are received from a human organ. These inputs come from the organ itself. DSP processors, because of their multidimensional data processing nature, are the electrical components that take up the greatest space and use the most power. In this age of digital technology and electronic gizmos, portable biomedical devices represent an essential step forward in technological advancement. Electrocardiogram (ECG) units are among the most common types of biomedical equipment, and their functions are absolutely necessary to the process of saving human life. In the latter part of the 1990s, portable electrocardiogram (ECG) devices began to appear on the market, and research into their signal processing and electronics design capabilities continues today. System-on-chip (SoC) design refers to the process through which the separate computing components of a DSP unit are combined onto a single chip in order to achieve greater power and space efficiency. In the design of biomedical DSP devices, this body of research presents a number of different solutions for reducing power consumption and space requirements. Using serial or parallel data buses, which are often the region that consumes the most power, it is possible to send data between the system-on-chip (SoC) and other components. To cut down on the number of needless switching operations that take place during data transmission, a hybrid solution that makes use of the shift invert bus encoding scheme has been developed. Using a phase-encoded shift invert bus encoding approach, which embeds the two-bit indication lines into a single-bit encoded line, is one way to solve the issue of having two distinct indicator bits. This method reduces the problem. The PESHINV approach is compared to the SHINV method that already exists, and the comparison reveals that the suggested PESHINV method reduces the total power consumption of the encoding circuit by around 30 percent. The computing unit of the DSP processor is the target of further optimization efforts. Virtually, all signal processing methods need memory and multiplier circuits to function properly.

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Mechanistic Insights into the Ligand-Induced Unfolding of an RNA G-Quadruplex

Cited by 44 publications

References 108 publications

G-Tetrad-Selective Ligand Binding Kinetics in G-Quadruplex DNA Probed with Fluorescence Correlation Spectroscopy

G-Tetrad-Selective Ligand Binding Kinetics in G-Quadruplex DNA Probed with Fluorescence Correlation Spectroscopy

Characterization of G-Quadruplexes in Enterovirus A71 Genome and Their Interaction with G-Quadruplex Ligands

Cryptography-Based Medical Signal Securing Using Improved Variation Mode Decomposition with Machine Learning Techniques

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