Denaturation of Drew–Dickerson DNA in a high salt concentration medium: Molecular dynamics simulations

Izanloo, Cobra; Parsafar, Gholamabbas; Abroshan, Hadi; Akbarzadeh, Hamed

doi:10.1002/jcc.21908

Cited by 10 publications

(9 citation statements)

References 55 publications

(59 reference statements)

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“…Several experimental studies indicate that indeed left-handed forms of DNA can occur in strongly supercoiled DNA [23,24,30]. Consistent with previous studies on base pair formation and melting [41,42,43] we found also an…”

Section: Plos Onesupporting

confidence: 92%

How global DNA unwinding causes non-uniform stress distribution and melting of DNA

Liebl

Zacharias

2020

PLoS ONE

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DNA unwinding is an important process that controls binding of proteins, gene expression and melting of double-stranded DNA. In a series of all-atom MD simulations on two DNA molecules containing a transcription start TATA-box sequence we demonstrate that application of a global restraint on the DNA twisting dramatically changes the coupling between helical parameters and the distribution of deformation energy along the sequence. Whereas only short range nearest-neighbor coupling is observed in the relaxed case, long-range coupling is induced in the globally restrained case. With increased overall unwinding the elastic deformation energy is strongly non-uniformly distributed resulting ultimately in a local melting transition of only the TATA box segment during the simulations. The deformation energy tends to be stored more in cytidine/guanine rich regions associated with a change in conformational substate distribution. Upon TATA box melting the deformation energy is largely absorbed by the melting bubble with the rest of the sequences relaxing back to near B-form. The simulations allow us to characterize the structural changes and the propagation of the elastic energy but also to calculate the associated free energy change upon DNA unwinding up to DNA melting. Finally, we design an Ising model for predicting the local melting transition based on empirical parameters. The direct comparison with the atomistic MD simulations indicates a remarkably good agreement for the predicted necessary torsional stress to induce a melting transition, for the position and length of the melted region and for the calculated associated free energy change between both approaches.

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Section: Plos Onesupporting

confidence: 92%

How global DNA unwinding causes non-uniform stress distribution and melting of DNA

Liebl

Zacharias

2020

PLoS ONE

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“…In this context, computer simulations could bring about a major productivity leap, providing thermodynamic and kinetic information on transition intermediates that might escape spectroscopic detection. Indeed, the large amount of molecular dynamics (MD) work on the melting of base pairs in various conditions (13, 26–37) suggests that base-pair opening is an asynchronous process, with one base unstacking significantly before the other. However, systematic studies on how the nucleic acid sequence can affect base-pair opening intermediates during the unzipping of ss/ds junctions are lacking.…”

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confidence: 99%

Asymmetric base-pair opening drives helicase unwinding dynamics

Colizzi

Pérez‐González

Fritzen

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.

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“…1, it is obvious that the RMSD increases with the increase in temperature. The simulation was performed for 50 ns at a temperatures of 280, 300, 320, 340, 360, 380, and 400 K. Moreover, unlike the other alternative temperatures, a gap in the RMSD can be seen in the last steps of the simulation between T = 340 and T = 360 K. The experimentally measured melting temperature of Dickerson DNA, in the presence of 1 mol/L NaCl, is 341 K. 38 Based on the simulation, the melting temperature obtained by Izanloo et al is reported as 349 K. 31 Schematic snapshots of DNA extracted from the MD simulation at seven different temperatures are shown in Fig. 2.…”

Section: Resultsmentioning

confidence: 86%

“…Area under the curve of the RDF for water hydrogen and negatively charged phosphate oxygen pairs at seven different temperatures for guanine (GUA), cytosine (CYT), thymine (THY), and adenine (ADE) bases. 31 According to the results presented in Table 1, by increasing the temperature, the number of water molecules around the phosphate oxygen atoms decreased but this was not sharp at T m . Therefore, the release of water molecules around the phosphate oxygen atoms could not be responsible for the sharpness of the transition curve, but the hydrogen bonds between the phosphate oxygen atoms and surrounding water molecules could be involved in the stability of .…”

Section: Figmentioning

confidence: 82%

“…47 The negative ⌬n w for ADE5:N7 is probably due to the stability of DNA in the environment with high concentrations of salt. 31 The final question is whether the simulation time, 50 ns, is sufficient for obtaining reliable RDF for sodium ion and water molecules or not. To answer to this question, the RDFs for 30, 40, and 50 ns segments of the simulation time were calculated.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of changes in the arrangement of water molecules and salt ions surrounding different atoms of the DNA molecule during the melting process: a molecular dynamics simulation study

Izanloo

2015

Can. J. Chem.

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A molecular dynamics simulation was performed on a B-DNA duplex (CGCGAATTGCGC) at different temperatures. The DNA was immerged in a saltwater medium with 1 mol/L NaCl concentration. The arrangements of water molecules and cations around the different atoms of DNA on the melting pathway were investigated. Almost for all atoms of the DNA by double helix ¡ single-stranded transition, the water molecules released from the DNA duplex and cations were close to single-stranded DNA, but this behavior was not clearly seen at melting temperatures. Therefore, release of water molecules and cations approaching the DNA by the increase of temperature does not have any effect on the sharpness of the transition curve. Most of the water molecules and cations were found to be around the negatively charged phosphate oxygen atoms. The number of water molecules released from the first shell hydration upon melting in the minor groove was higher than in the major groove, and intrusion of cations into the minor groove after melting was higher than into the major groove. The hydrations of imino protons were different from each other and were dependent on DNA bases.Résumé : Nous avons exécuté la simulation de dynamique moléculaire d'une séquence d'ADN B bicaténaire (CGCGAATTGCGC) à différentes températures. L'ADN était immergé dans un milieu aqueux salin dont la concentration en NaCl était de 1 mol/L. On a étudié la disposition des molécules d'eau et des cations autour des différents atomes d'ADN durant le processus de dénatur-ation. Du point de vue de presque tous les atomes d'ADN situés dans le voisinage de l'endroit où se produit le désapariement lors de la transition de l'ADN bicaténaire en ADN monocaténaire, les molécules d'eau libérées de l'ADN bicaténaire et les cations se trouvaient à proximité de l'ADN simple brin. Or, ce comportement n'était pas clairement observable du point de vue des températures de dénaturation. Par conséquent, la libération des molécules d'eau et des cations dans le voisinage de l'ADN entraînée par une augmentation de température n'a aucun effet sur la netteté de la courbe de transition. La majeure partie des molécules d'eau et des cations se trouvait autour des atomes d'oxygène des groupements phosphates, chargés négativement. Au moment de la dénaturation, les molécules d'eau de la première couche d'hydratation étaient libérées en plus grand nombre du petit sillon que du grand sillon, et l'intrusion des cations après la dénaturation était plus importante dans le petit sillon que dans grand le sillon. Les degrés d'hydratation des protons des groupements imines différaient les uns des autres en fonction des bases de l'ADN. [Traduit par la Rédaction] Mots-clés : ADN, fonction de distribution radiale, dénaturation de l'ADN, dynamique moléculaire.

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Denaturation of Drew–Dickerson DNA in a high salt concentration medium: Molecular dynamics simulations

Cited by 10 publications

References 55 publications

How global DNA unwinding causes non-uniform stress distribution and melting of DNA

How global DNA unwinding causes non-uniform stress distribution and melting of DNA

Asymmetric base-pair opening drives helicase unwinding dynamics

Investigation of changes in the arrangement of water molecules and salt ions surrounding different atoms of the DNA molecule during the melting process: a molecular dynamics simulation study

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