Molecular Dynamics Simulations of Duplex Stretching Reveal the Importance of Entropy in Determining the Biomechanical Properties of DNA

Harris, Sarah A.; Sands, Zara A.; Laughton, Charles A.

doi:10.1529/biophysj.104.046912

Cited by 88 publications

(121 citation statements)

References 38 publications

(59 reference statements)

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“…In Ref. [12] large scale molecular dynamics calculations indicate the formation of denaturing bubbles when pure DNA is stretched above 65 pN forces. Since we use very small stretching forces it is likely that the abrupt transition we observe is caused by some intrinsic DNA structural changes induced by the intercalating drug.…”

Section: Figmentioning

confidence: 99%

DNA-psoralen: Single-molecule experiments and first principles calculations

Rocha

Lúcio

Alexandre

et al. 2009

Applied Physics Letters

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The authors measure the persistence and contour lengths of DNA-psoralen complexes, as a function of psoralen concentration, for intercalated and crosslinked complexes. In both cases, the persistence length monotonically increases until a certain critical concentration is reached, above which it abruptly decreases and remains approximately constant. The contour length of the complexes exhibits no such discontinuous behavior. By fitting the relative increase of the contour length to the neighbor exclusion model, we obtain the exclusion number and the intrinsic intercalating constant of the interaction. Ab initio calculations are employed in order to provide an atomistic picture of these experimental findings.

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Section: Figmentioning

confidence: 99%

DNA-psoralen: Single-molecule experiments and first principles calculations

Rocha

Lúcio

Alexandre

et al. 2009

Applied Physics Letters

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“…The structure of the overstretched state of the DNA is not yet fully resolved and is under intense debate [8,9,14,[32][33][34][35][38][39][40] over the last two decades. Thus it is still an open question whether the overstretching transition leads to FIM or gives rise to S-DNA.…”

Section: Introductionmentioning

confidence: 99%

Overstretching of B-DNA with various pulling protocols: Appearance of structural polymorphism and S-DNA

Garai

Mogurampelly

Bag

et al. 2017

The Journal of Chemical Physics

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We report a structural polymorphism of the S-DNA when a canonical B-DNA is stretched under different pulling protocols and provide a fundamental molecular understanding of the DNA stretching mechanism. Extensive all atom molecular dynamics simulations reveal a clear formation of S-DNA when the B-DNA is stretched along the 3 ′ directions of the opposite strands (OS3) and is characterized by the changes in the number of H-bonds, entropy and free energy. Stretching along 5 ′ directions of the opposite strands (OS5) leads to force induced melting form of the DNA.Interestingly, stretching along the opposite ends of the same strand (SS) leads to a coexistence of both the S-and melted M-DNA structures. We also do the structural characterization of the S-DNA by calculating various helical parameters. We find that S-DNA has a twist of ∼ 10 degrees which corresponds to helical repeat length of ∼ 36 base pairs in close agreement with the previous experimental results. Moreover, we find that the free energy barrier between the canonical and overstretched states of DNA is higher for the same termini (SE) pulling protocol in comparison to all other protocols considered in this work. Overall, our observations not only reconcile with the available experimental results qualitatively but also enhance the understanding of different overstretched DNA structures.

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“…Initially, steered MD simulations of torsionally unconstrained DNA molecules were employed [16,17,[26][27][28][29]. According to this approach, the overstretching experiments are simulated taking explicitly into account the presence of a pulling force.…”

Section: Introductionmentioning

confidence: 99%

The transition mechanism of DNA overstretching: a microscopic view using molecular dynamics

Bongini

Lombardi

Bianco

2014

J. R. Soc. Interface.

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The overstretching transition in torsionally unconstrained DNA is studied by means of atomistic molecular dynamics simulations. The free-energy profile as a function of the length of the molecule is determined through the umbrella sampling technique providing both a thermodynamic and a structural characterization of the transition pathway. The zero-force free-energy profile is monotonic but, in accordance with recent experimental evidence, becomes two-state at high forces. A number of experimental results are satisfactorily predicted: (i) the entropic and enthalpic contributions to the free-energy difference between the basic (B) state and the extended (S) state; (ii) the longitudinal extension of the transition state and (iii) the enthalpic contribution to the transition barrier. A structural explanation of the experimental finding that overstretching is a cooperative reaction characterized by elementary units of approximately 22 base pairs is found in the average distance between adenine/thymine-rich regions along the molecule. The overstretched DNA adopts a highly dynamical and structurally disordered double-stranded conformation which is characterized by residual base pairing, formation of non-native intra-strand hydrogen bonds and effective hydrophobic screening of apolar regions.

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Molecular Dynamics Simulations of Duplex Stretching Reveal the Importance of Entropy in Determining the Biomechanical Properties of DNA

Cited by 88 publications

References 38 publications

DNA-psoralen: Single-molecule experiments and first principles calculations

DNA-psoralen: Single-molecule experiments and first principles calculations

Overstretching of B-DNA with various pulling protocols: Appearance of structural polymorphism and S-DNA

The transition mechanism of DNA overstretching: a microscopic view using molecular dynamics

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