CD-NuSS: A Web Server for the Automated Secondary Structural Characterization of the Nucleic Acids from Circular Dichroism Spectra Using Extreme Gradient Boosting Decision-Tree, Neural Network and Kohonen Algorithms

Sathyaseelan, Chakkarai; Vijayakumar, Vinothini; Rathinavelan, Thenmalarchelvi

doi:10.1016/j.jmb.2020.08.014

Cited by 21 publications

(18 citation statements)

References 28 publications

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“…However, there are now sophisticated analysis tools available that allow deconvolution of complex CD spectra from polymorphic G4s. [103,104] Time-resolved CD spectroscopy was used in combination with an laser-induced temperature jump to monitor G4 folding down to a millisecond timescale. [77] UV spectroscopy is suited as a readout in a similar way, but is restricted to a simple "folded/non-folded" monitoring with characteristic changes at 295 nm.…”

Section: Circular Dichroismmentioning

confidence: 99%

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Folding dynamics of polymorphic G‐quadruplex structures

Grün

Schwalbe

2021

Biopolymers

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G-quadruplexes (G4), found in numerous places within the human genome, are involved in essential processes of cell regulation. Chromosomal DNA G4s are involved for example, in replication and transcription as first steps of gene expression. Hence, they influence a plethora of downstream processes. G4s possess an intricate structure that differs from canonical B-form DNA. Identical DNA G4 sequences can adopt multiple long-lived conformations, a phenomenon known as G4 polymorphism. A detailed understanding of the molecular mechanisms that drive G4 folding is essential to understand their ambivalent regulatory roles.Disentangling the inherent dynamic and polymorphic nature of G4 structures thus is key to unravel their biological functions and make them amenable as molecular targets in novel therapeutic approaches. We here review recent experimental approaches to monitor G4 folding and discuss structural aspects for possible folding pathways. Substantial progress in the understanding of G4 folding within the recent years now allows drawing comprehensive models of the complex folding energy landscape of G4s that we herein evaluate based on computational and experimental evidence.

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Section: Circular Dichroismmentioning

confidence: 99%

“…[112] This powerful method in combination with advanced computational methods for the deconvolution of CD spectroscopical and mass spectrometric parameters will enable new perspectives on G4 folding. [104,[113][114][115][116]…”

Section: Mass Spectrometrymentioning

confidence: 99%

Folding dynamics of polymorphic G‐quadruplex structures

Grün

Schwalbe

2021

Biopolymers

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“…The unit sequence of the control DNA (5´-GGG TCT AAG GGC TCG AGG GTC TGC GGG-3') showed an expected positive peak around 210 nm in the CD spectra (Fig S4A). The negative peak at around 240 nm and the positive peaks at 260 nm and 290 nm further confirmed the formation of hybrid G4s 43,44 . These signature peaks were absent in a control WC sequence (Fig S4B ), indicating that the hybrid quadruplex formation was specific to Scheme-DG and not observed in the Scheme-WC.…”

Section: An Application Of Abc G4-chip Identifies Cggbp1 As An Agent ...mentioning

confidence: 59%

G-quadruplex landscape and its regulation revealed by a new antibody capture method

Datta

Patel

Sathyaseelan

et al. 2022

Preprint

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Our understanding of DNA G-quadruplexes (G4s) from in vitro studies has been complemented by genome-wide G4 landscapes from cultured cells. Conventionally, formation of G4s is accepted to depend on G-repeats such that they form tetrads. However, genome-wide G4s characterized through high-throughput sequencing suggests that these structures form at a large number of regions with no such canonical G4-forming signatures. New functions, such as regulation of gene expression regulation and replication have been attributed to the genomic G4s. Many G4-binding proteins have been described, but their roles in formation and maintenance of G4s remain unknown. The representation of G4s not bound to proteins in these genomic landscapes remains unaddressed. We have developed a simple variation of the conventional G4-chromatin immunoprecipitation (G4-ChIP) assay to capture G4s in the cells using the 1H6 antibody. A comparison with the conventional G4-ChIP and in vitro DNA pull-down assays shows that our method minimizes false G4 detection. We use this method along with a transfected or in vitro-added control DNA (containing canonical G4-forming sequences) to study the G4 regulatory effects of the CGG repeat-binding protein CGGBP1. We present a reliable G4 landscape and apply the new protocol to discover a functionally relevant regulation of G4s by CGGBP1. Our results show that sharp interstrand transitions of G/C-skew, rich in binding sites for CTCF and CGGBP1, form G4s. Thus, our method demonstrates a sequence property-specific constraints of the nuclear environment that mitigates G4 formation.

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“…For the DNA duplex…hZα ADAR1 titration, the protein (P)/nucleic acids (N) ratios of 0, 0.50, 0.75, 1:1, 1:2, 1:3 and 1:4 were used by keeping the DNA concentration as a constant (40 μM). The CD data was analyzed through spectra manager software (www.jasco inc.com) and verified with the reference dataset of CD-NuSS webserver 56 . www.nature.com/scientificreports/ the range of 0-5 (Schemes WC, DCA1 to DCA5) were used.…”

Section: Simulation Setupmentioning

confidence: 99%

Spontaneous and frequent conformational dynamics induced by A…A mismatch in d(CAA)·d(TAG) duplex

Ajjugal

Tomar

Rao

et al. 2021

Sci Rep

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Base pair mismatches in DNA can erroneously be incorporated during replication, recombination, etc. Here, the influence of A…A mismatch in the context of 5′CAA·5′TAG sequence is explored using molecular dynamics (MD) simulation, umbrella sampling MD, circular dichroism (CD), microscale thermophoresis (MST) and NMR techniques. MD simulations reveal that the A…A mismatch experiences several transient events such as base flipping, base extrusion, etc. facilitating B–Z junction formation. A…A mismatch may assume such conformational transitions to circumvent the effect of nonisostericity with the flanking canonical base pairs so as to get accommodated in the DNA. CD and 1D proton NMR experiments further reveal that the extent of B–Z junction increases when the number of A…A mismatch in d(CAA)·d(T(A/T)G) increases (1–5). CD titration studies of d(CAA)·d(TAG)n=5 with the hZαADAR1 show the passive binding between the two, wherein, the binding of protein commences with B–Z junction recognition. Umbrella sampling simulation indicates that the mismatch samples anti…+ syn/+ syn…anti, anti…anti & + syn…+ syn glycosyl conformations. The concomitant spontaneous transitions are: a variety of hydrogen bonding patterns, stacking and minor or major groove extrahelical movements (with and without the engagement of hydrogen bonds) involving the mismatch adenines. These transitions frequently happen in anti…anti conformational region compared with the other three regions as revealed from the lifetime of these states. Further, 2D-NOESY experiments indicate that the number of cross-peaks diminishes with the increasing number of A…A mismatches implicating its dynamic nature. The spontaneous extrahelical movement seen in A…A mismatch may be a key pre-trapping event in the mismatch repair due to the accessibility of the base(s) to the sophisticated mismatch repair machinery.

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CD-NuSS: A Web Server for the Automated Secondary Structural Characterization of the Nucleic Acids from Circular Dichroism Spectra Using Extreme Gradient Boosting Decision-Tree, Neural Network and Kohonen Algorithms

Cited by 21 publications

References 28 publications

Folding dynamics of polymorphic G‐quadruplex structures

Folding dynamics of polymorphic G‐quadruplex structures

G-quadruplex landscape and its regulation revealed by a new antibody capture method

Spontaneous and frequent conformational dynamics induced by A…A mismatch in d(CAA)·d(TAG) duplex

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