Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA

Sharma, Dinesh C; Sharma, Kopal; Mishra, Aashwin; Siwach, Priyanka; Mittal, Aditya; Jayaram, B.

doi:10.1039/d2cp04820e

Cited by 2 publications

(1 citation statement)

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“…They anticipated that low-affinity binding sites can increase binding and proposed the STRs function as “rheostats” to tune local TF concentration and binding responses (35). Another research pointed out that the molecular dynamics-derived trinucleotide and tetranucleotide-based structure and energy parameters exist in a signature profile at the transcription start sites region of both prokaryotes and eukaryotes (36). However, the mechanism by which eukaryotic TFs find their target through flanking DNA has not been characterized, experimentally observed, or demonstrated at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

DNA-protein interaction is dominated by short anchoring elements

Chen,

Xu,

et al. 2023

Preprint

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To understand the regulation of gene expression, it is essential to elucidate the binding mechanism of DNA binding domain (DBD) of transcription factors (TFs), and predict the location of transcription factor binding sites (TFBSs). For an exhaustive search of TFBSs, we have investigated four typical TFs with diverse origins, such as WRKY, PU.1, GLUCOCORTICOID RECEPTOR (GR), and MYC2 by using a newly developed method, KaScape. During KaScape experiments, we identified short sequences (3-4 bases) or “anchoring element” (AE) for the four TFs that dominated the bound population of DNA-DBD binding. We further developed the AEEscape (AE Energy landscape) algorithm to detect and confirm the AE and derived its binding energy landscape for all possible sequences. Our analysis of the energy landscape revealed an energetic funnel around the TFBS, which is related to the AE density gradient in the region surrounding the TFBS. Our results provide novel insights into the mechanism of TF binding to TFBSs.

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Section: Introductionmentioning

confidence: 99%

DNA-protein interaction is dominated by short anchoring elements

Chen,

Xu,

et al. 2023

Preprint

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Exon-Intron Boundary Detection Made Easy by Physicochemical Properties of DNA

Jayaram,

Sharma,

Aslam

et al. 2024

Preprint

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Genome architecture in eukaryotes exhibits a high degree of complexity. Amidst the numerous intricacies, the existence of genes as non-continuous stretches composed of exons and introns has garnered significant attention and curiosity among researchers. Accurate identification of exon-intron boundary junctions is crucial to decipher the molecular biology governing gene expression of regular and aberrant splicing. The currently employed frameworks for genomic signals, which aim to identify exons and introns within a genomic segment, need to be revised primarily due to the lack of a robust consensus sequence and the limitations posed by the training on available experimental data sets. To tackle these challenges and capitalize on the understanding that deoxyribonucleic acid (DNA) exhibits function-dependent local structural and energetic variations, we present ChemEXIN, an innovative method for predicting exon-intron boundaries. The method utilizes a deep-learning (DL) model alongside tri- and tetra-nucleotide-based structural and energy parameters. ChemEXIN surpasses current methods in accuracy and reliability. Our work represents a significant advancement in exon-intron boundary annotations, with potential implications for understanding gene expression, regulation, and biomedical research.

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Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA

Abstract: Genomes of most of the organisms on earth are written in a universal language of life, made up of four units – Adenine (A), Thymine (T), Guanine (G), and Cytosine...

Cited by 2 publications

References 81 publications

DNA-protein interaction is dominated by short anchoring elements

DNA-protein interaction is dominated by short anchoring elements

Exon-Intron Boundary Detection Made Easy by Physicochemical Properties of DNA

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