Evaluation of the Gibbs Free Energy Changes and Melting Temperatures of DNA/DNA Duplexes Using Hybridization Enthalpy Calculated by Molecular Dynamics Simulation

Lomzov, Alexander A.; Vorobjev, Yury N.; Pyshnyi, D. V.

doi:10.1021/acs.jpcb.5b09645

Cited by 35 publications

(41 citation statements)

References 79 publications

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“…Finally, using a very similar force field to that used here, the Pyshnyi group recently reported MD simulations of a very large number of ssDNA and dsDNA oligonucleotides, and showed that they could be used to calculate duplex hybridization enthalpies that were in very good agreement with experimental values. 86 …”

Section: Discussionmentioning

confidence: 99%

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Andrews

Campbell

Elcock

2017

J. Chem. Theory Comput.

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Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid sidechains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of twenty amino acid sidechain analogs interacting simultaneously with both a 70-base pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid sidechains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged sidechains, all types of amino acid sidechain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic sidechains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged sidechains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged sidechains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt-dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

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Section: Discussionmentioning

confidence: 99%

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Andrews

Campbell

Elcock

2017

J. Chem. Theory Comput.

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“…35–37 This model separates the DNA into three sites per nucleotide, one each for the phosphate, sugar, and base, and has been parametrized to reproduce correct structural, thermodynamic, mechanical, and kinetic properties of DNA. Assuming incompressibility, we computed the enthalpy of duplex formation as 38 …”

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confidence: 99%

The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization

Fong¹,

Wang²,

Schatz³

et al. 2018

J. Am. Chem. Soc.

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DNA hybridization onto DNA-functionalized nanoparticle surfaces (e.g., in the form of a spherical nucleic acid (SNA)) is known to be enhanced relative to hybridization free in solution. Surprisingly, via isothermal titration calorimetry, we reveal that this enhancement is enthalpically, as opposed to entropically, dominated by ~20 kcal/mol. Coarse-grained molecular dynamics simulations suggest that the observed enthalpic enhancement results from structurally confining the DNA on the nanoparticle surface and preventing it from adopting enthalpically unfavorable conformations like those observed in the solution case. The idea that structural confinement leads to the formation of energetically more stable duplexes is evaluated by decreasing the degree of confinement a duplex experiences on the nanoparticle surface. Both experiment and simulation confirm that when the surface-bound duplex is less confined, i.e., at lower DNA surface density or at greater distance from the nanoparticle surface, its enthalpy of formation approaches the less favorable enthalpy of duplex formation for the linear strand in solution. This work provides insight into one of the most important and enabling properties of SNAs and will inform the design of materials that rely on the thermodynamics of hybridization onto DNA-functionalized surfaces, including diagnostic probes and therapeutic agents.

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“…Hybridization thermodynamics at the atomistic scale has been studied in more recent recent work, in addition to the work by Piana 22 mentioned in the Introduction. In a study by Lomzov et al, 61 DNA melting temperature is calculated from the difference in the total energy of hybridized and that of unhybridized states, assuming that i) the volume change upon hybridization is negligible, ii) the difference in total energy of double-stranded state and that of single-stranded state is the same as the hybridization enthalpy when the assumption i)…”

Section: Discussionmentioning

confidence: 99%

Thermodynamics of DNA Hybridization from Atomistic Simulations

Zerze

Stillinger²,

Debenedetti

2020

Preprint

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Studying the DNA hybridization equilibrium via brute force molecular dynamics (MD) or commonly used advanced sampling approches is notoriously difficult at atomistic lengthscale. However, besides providing a more realistic modeling of this microscopic phenomenon, atomistic resolution is a necessity for some fundamental research questions, such as the ones related to DNA’s chirality. Here, we describe an order parameter-based advanced sampling technique to calculate the free energy surface of hybridization and estimate melting temperature of DNA oligomers at atomistic resolution, using a native topology-based order parameter. We show that the melting temperatures estimated from our atomistic simulations follow an order consistent with the predictions from melting experiments and those from the nearest neighbor model, for a range of DNA sequences of different GC content. Moreover, free energy surfaces and melting temperatures are calculated to be identical for D- and L-enantiomers of Drew-Dickerson dodecamer.Abstract FigureGraphical TOC Entry

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Evaluation of the Gibbs Free Energy Changes and Melting Temperatures of DNA/DNA Duplexes Using Hybridization Enthalpy Calculated by Molecular Dynamics Simulation

Cited by 35 publications

References 79 publications

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization

Thermodynamics of DNA Hybridization from Atomistic Simulations

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