Determination of ligand to DNA binding parameters from two-dimensional DSC curves

Dukhopelnikov, E. V.; Bereznyak, E. G.; Хребтова, А. С.; Лантушенко, А. О.; Zinchenko, A. V.

doi:10.1007/s10973-012-2561-6

Cited by 8 publications

(4 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the two-dimensional DSC curves). Comparison of the binding parameters calculated by fitting of two-dimensional DSC curves with the literature data and with that obtained by alternative experimental techniques, had demonstrated that the approach presented in [64] gives satisfactory results.…”

Section: Calorimetrymentioning

confidence: 84%

“…When the DNA-ligand system is being analysed, certain specificities of the complexation and melting of linear polymeric molecules should be taken into consideration. Recently a novel analytical approach for detailed analysis of the DNA-ligand interactions from DSC data was proposed [64]. The DNA macromolecule in this study is represented as an assembly of cooperative units, which melt according to the two-state model.…”

Section: Calorimetrymentioning

confidence: 99%

See 1 more Smart Citation

Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment

Evstigneev

Shestopalova

2014

Challenges and Advances in Computational Chemistry and Physics

View full text Add to dashboard Cite

In this chapter we demonstrate the large usefulness of using complex approach for understanding the mechanism of binding of biologically active compounds (antitumour antibiotics, mutagens etc.) with nucleic acids (NA). The applications of various biophysical methods and computer modeling to determination of structural (Infra-red and Raman vibrational spectroscopies, computer modeling by means of Monte-Carlo, molecular docking and molecular dynamics methods) and thermodynamic (UV-VIS spectrophotometry, microcalorimetry, molecular dynamics simulation) parameters of NA-ligand complexation with estimation of the role of water environment in this process, are discussed. The strategy of energy analysis of the NA-ligand binding reactions in solution is described, which is based on decomposition of experimentally measured net Gibbs free energy of binding in terms of separate energetic contributions from particular physical factors. The main outcome of such analysis is to answer the questions "What physical factors and to what extent stabilize/destabilize NA-ligand complexes?" and "What physical factors most strongly affect the bioreceptor binding affinity?"

show abstract

Section: Calorimetrymentioning

confidence: 84%

Section: Calorimetrymentioning

confidence: 99%

Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment

Evstigneev

Shestopalova

2014

Challenges and Advances in Computational Chemistry and Physics

View full text Add to dashboard Cite

show abstract

“…To describe the melting of DNA-ligand complex we use the approach proposed earlier for differential scanning calorimetry data analysis and based on the equations of chemical equilibrium [4] . In this approach the melting of complex is considered as two independent equilibrium processes: the complex dissociation and the DNA denaturation.…”

mentioning

confidence: 99%

“…The size of the cooperative unit of natural DNA is about 25 base pairs [4]. The complex formation is described as stepwise saturation of the cooperative unit by the ligand molecules.…”

mentioning

confidence: 99%

Thermodynamic analysis of ligand - DNA complex formation from the spectrophotometric data

Anastasiia

2015

2015 International Young Scientists Forum on Applied Physics (YSF)

View full text Add to dashboard Cite

DNA is the target for many anticancer and antitumor drugs. Therefore determination of the thermodynamic parameters of ligands -DNA interaction for prediction of biological activity at the molecular level is important in the current biophysical studies. Thermodynamic analysis of ligand -DNA complexation is based on the determination of the equilibrium binding constant (K bind ) as well as enthalpy (ΔH bind ) and entropy (ΔS bind ) contributions to the free energy.Spectrophotometry is one of the widely used experimental techniques to determine the binding parameters. The most ligands absorb the light in the visible region of spectrum. It allows to examine the spectral changes without DNA absorption band contribution (it maximum is at λ max ≈ 260 nm).A well known method of equilibrium binding constant calculation is the analysis of spectrophotometric titration data of ligand-DNA system by means of multiple complexation models [1].Determination of the binding enthalpy and entropy from spectrophotometric data usually is based on Vant-Hoff equation. It allows to obtain the values of these parameters by approximation of ln K bind dependence on the inverse temperature [2]. A set of values of the equilibrium constants K bind (T) is obtained from titration experiments carried out at various temperatures [1]. Also, the Vant-Hoff formalism can be applied for estimation of the binding enthalpy in the DNAligand system from the slope of molar absorption dependence on the inverse temperature directly. In this case the proportionality of binding constant and molar absorption is assumed and calculation of K bind values is not carried out [3].The main shortcoming of the approaches based on VantHoff equation is caused by the slight absorption changes in the temperature range before the melting of complex. It results in large errors of determination of binding enthalpy value.We propose the novel method to calculate the binding parameters in the DNA-ligand system in wide range of temperatures including DNA melting. It allows to improve the calculation accuracy because the significant changes in absorption spectra are observed exactly in the melting temperature range.To describe the melting of DNA-ligand complex we use the approach proposed earlier for differential scanning calorimetry data analysis and based on the equations of chemical equilibrium [4] . In this approach the melting of complex is considered as two independent equilibrium processes: the complex dissociation and the DNA denaturation.The polymeric DNA macromolecule is represented as an assembly of cooperative units that melt by two-state model. The size of the cooperative unit of natural DNA is about 25 base pairs [4]. The complex formation is described as stepwise saturation of the cooperative unit by the ligand molecules. Statistical distribution of ligand molecules along the matrix and the temperature dependences of the melting and binding enthalpies as well as the constants of these processes are taken into account.As a result we have a system of equations that allow...

show abstract

Determination of ligand to DNA binding parameters from two-dimensional DSC curves

Cited by 8 publications

References 51 publications

Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment

Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment

Thermodynamic analysis of ligand - DNA complex formation from the spectrophotometric data

Related Topics in Calorimetry

Contact Info

Product

Resources

About