139 Analysis of structure and thermodynamics of modified DNA duplexes using molecular dynamics simulation

Lomzov, Alexander A.; Gorelov, Vitaly V.; Golyshev, Victor M.; Abramova, Tatiana; Пышный, Д. В.

doi:10.1080/07391102.2015.1032772

Cited by 3 publications

(2 citation statements)

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“…The thermodynamic stability of the matched th G-labeled duplexes was estimated by the molecular mechanics Poisson− Boltzmann surface area (MM-PBSA) approach by calculating the delta energy of binding, ΔE b (Table 2), which corresponds to the difference in total energy between the duplexes and their constitutive single-stranded sequences and is thus related to the hybridization enthalpy. 42 The duplex stability was also characterized by its melting temperature T m , either determined experimentally with the th G-labeled duplexes from the temperature dependence of their absorbance changes at 260 nm (Figure S6) or predicted by DINAMelt 43 on the corresponding unlabeled duplexes (Table 2). Interestingly, an excellent match was found between the experimental and the DINAMelt-predicted T m values, confirming that substitution of G by th G does not impact the melting temperature in DNA duplexes.…”

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confidence: 99%

What Makes Thienoguanosine an Outstanding Fluorescent DNA Probe?

et al. 2020

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Thienoguanosine ( th G) is an isomorphic guanosine (G) surrogate that almost perfectly mimics G in nucleic acids. To exploit its full potential and lay the foundation for future applications, twenty DNA duplexes, where the bases facing and neighboring th G were systematically varied, were thoroughly studied using fluorescence spectroscopy, molecular dynamics simulations and mixed quantum mechanical/molecular mechanics calculations, yielding a comprehensive understanding of its photophysics in DNA. In matched duplexes, th G's hypochromism was larger for flanking G/C residues but its fluorescence quantum yield (QY) and lifetime values were almost independent of the flanking bases. This was attributed to high duplex stability, which maintains a steady orientation and distance between nucleobases, so that a similar charge transfer (CT) mechanism governs the photophysics of th G independently of its flanking nucleobases. th G can therefore replace any G residue in matched duplexes, while always maintaining similar photophysical features. In contrast, the local destabilization induced by a mismatch or an abasic site restores a strong dependence of th G's QY and lifetime values on its environmental context, depending on the CT route efficiency and solvent exposure of th G. Due to this exquisite sensitivity, th G appears ideal for monitoring local structural changes and single nucleotide polymorphism.Moreover, th G's dominant fluorescence lifetime in DNA is unusually long (9-29 ns), facilitating its selective measurement in complex media using a lifetime-based or a time-gated detection *

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Section: Resultsmentioning

confidence: 99%

What Makes Thienoguanosine an Outstanding Fluorescent DNA Probe?

et al. 2020

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“…These methods of estimating the energy of intermolecular interactions are widely used when studying the interactions of biopolymers with small molecules, e.g., in molecular biological studies [28] or the development of new drugs [29]. The successful application of these approaches has also been demonstrated for calculation of the energy of complex formation with DNA and RNA of both native [30,31] and chemically modified oligonucleotides [32][33][34][35][36]. However, in the latter case, the research is not systematic; it is rather an illustration of the possibilities of the methods.…”

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Calculation of Energy for RNA/RNA and DNA/RNA Duplex Formation by Molecular Dynamics Simulation

2021

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The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy ($$\Delta G_{{37}}^{^\circ }$$ ) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the $$\Delta G_{{37}}^{^\circ }$$ of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

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