Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding

Gravina, Nicholas M; Gumbart, James C.; Kim, Harold D.

doi:10.1021/acs.jpcb.1c00432

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…oxDNA, a simulation platform to implement the coarse‐grained DNA model, has been widely used for describing a wide variety of biophysical properties of DNA, characterizing a number of DNA nanostructures. [ 31 ] First, the distance distribution of bases a and b which tend to bind was investigated through long‐term analysis of structural movements (Figure 1B). In this process, we mainly analyzed the distance variation of the two complementary bases selected on the probe from the initial relaxation conformation to the stable hybridization binding.…”

Section: Resultsmentioning

confidence: 99%

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Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Kou

Wang

Zhang

et al. 2022

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DNA‐based nanodevices equipped with localized modules have been promising probes for biomarker detection. Such devices heavily rely on the intramolecular hybridization reaction. However, there is a lack of mechanistic insights into this reaction that limits the sensing speed and sensitivity. A coarse‐grained model is utilized to simulate the intramolecular hybridization of localized DNA circuits (LDCs) not only optimizing the performance, but also providing mechanistic insights into the hybridization reaction. The simulation guided‐LDCs enable the detection of multiple biomarkers with high sensitivity and rapid speed showing good consistency with the simulation. Fluorescence assays demonstrate that the simulation‐guided LDC shows an enhanced sensitivity up to 9.3 times higher than that of the same probes without localization. The detection limits of ATP, miRNA, and APE1 reach 0.14 mM, 0.68 pM, and 0.0074 U mL−1, respectively. The selected LDC is operated in live cells with good success in simultaneously detecting the biomarkers and discriminating between cancer cells and normal cells. LDC is successfully applied to detect the biomarkers in cancer tissues from patients, allowing the discrimination of cancer/adjacent/normal tissues. This work herein presents a design workflow for DNA nanodevices holding great potential for expanding the applications of DNA nanotechnology in diagnostics and therapeutics.

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Section: Resultsmentioning

confidence: 99%

“…It was reported that the studied biomarkers are abnormally expressed in NSCLC. [ 26–53 ] We collected 10 groups of clinical samples. Every group included tumor tissues, tumor‐adjacent tissues, and normal control tissues of NSCLC patients ( Figure A).…”

Section: Resultsmentioning

confidence: 99%

Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Kou

Wang

Zhang

et al. 2022

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“…With our bow design, x 0 also corresponds to the equilibrium extension of the ssDNA bow-string, and therefore its value will depend on both the bow size as well as whether the probe is bound to the complementary target segment. To find a realistic value of x 0 , we performed oxDNA2 simulations [53-55] for all possible combinations of bow size, target sequence, and probe state (bound or unbound). DNA bows bound to an RNA probe were not simulated; while oligomeric RNA-DNA duplexes have a slightly smaller helical rise [56], the overall effect that this difference would have on the force is negligible.…”

Section: Methodsmentioning

confidence: 99%

Weak tension accelerates hybridization and dehybridization of short oligonucleotides

Hart

Jeong

Gumbart

et al. 2022

Preprint

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The hybridization and dehybridization of DNA subject to tension is relevant to fundamental genetic processes and to the design of DNA-based mechanobiology assays. While strong tension accelerates DNA melting and decelerates DNA annealing, the effects of tension weaker than 5 pN are less clear. In this study, we developed a DNA bow assay, which uses the bending rigidity of double-stranded DNA (dsDNA) to exert weak tension on a single-stranded DNA (ssDNA) target in the range of 2pN to 6pN. Combining this assay with single-molecule FRET, we measured the hybridization and dehybridization kinetics between a 15 nt ssDNA under tension and a 8-9 nt oligo, and found that both the hybridization and dehybridization rates monotonically increase with tension for various nucleotide sequences tested. These findings suggest that the nucleated duplex in its transition state is more extended than the pure dsDNA or ssDNA counterpart. Our simulations using the coarse-grained oxDNA2 model indicate that the increased extension of the transition state is due to exclusion interactions between unpaired ssDNA regions in close proximity to one another. This study highlights an example where the ideal worm-like chain models fail to explain the kinetic behavior of DNA in the low force regime.

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“…With our bow design, x 0 also corresponds to the equilibrium extension of the ssDNA bowstring, and therefore its value will depend on both the bow size as well as whether the probe is bound to the complementary target segment. To find a realistic value of x 0 , we performed oxDNA2 simulations [53][54][55] for all possible combinations of bow size, target sequence, and probe state (bound or unbound). DNA bows bound to an RNA probe were not simulated;…”

Section: B Dna Bow Assaymentioning

confidence: 99%

Weak tension accelerates hybridization and dehybridization of short oligonucleotides

Hart¹,

Jiyoun²,

Gumbart³

et al. 2022

Preprint

Self Cite

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The hybridization and dehybridization of DNA subject to tension is relevant to fundamental genetic processes and to the design of DNA-based mechanobiology assays. While strong tension accelerates DNA melting and decelerates DNA annealing, the effects of tension weaker than 5 pN are less clear. In this study, we developed a DNA bow assay, which uses the bending rigidity of double-stranded DNA (dsDNA) to exert weak tension on a single-stranded DNA (ssDNA) target in the range of 2 pN to 6 pN. Combining this assay with single-molecule FRET, we measured the hybridization and dehybridization kinetics between a 15 nt ssDNA under tension and a 8-9 nt oligo, and found that both the hybridization and dehybridization rates monotonically increase with tension for various nucleotide sequences tested. These findings suggest that the nucleated duplex in its transition state is more extended than the pure dsDNA or ssDNA counterpart. Our simulations using the coarse-grained oxDNA2 model indicate that the increased extension of the transition state is due to exclusion interactions between unpaired ssDNA regions in close proximity to one another. This study highlights an example where the ideal worm-like chain models fail to explain the kinetic behavior of DNA in the low force regime.

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Coarse-Grained Simulations of DNA Reveal Angular Dependence of Sticky-End Binding

Cited by 7 publications

References 56 publications

Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Weak tension accelerates hybridization and dehybridization of short oligonucleotides

Weak tension accelerates hybridization and dehybridization of short oligonucleotides

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