Electrostatic contribution to the energy of binding of aromatic ligands with DNA

Abstract

The method of solution of the nonlinear Poisson-Boltzmann equation was used to calculate electrostatic energy of binding of various aromatic ligands with DNA oligomers of different length. Analysis of the electrostatic contribution was made in terms of a two-step DNA binding process: formation of the intercalation cavity and insertion of the ligand. The total electrostatic energy was also partitioned into components: the energy of atom-atom coulombic interactions and the energy of interaction with surrounding water. The results indicate that electrostatic interactions are, as a whole, unfavorable to the intercalation process and that a correct analysis of structure-energy interrelation for Ligand-DNA interactions should only be accomplished at the level of the components rather than at the level of total electrostatic energy.

Energy analysis of non-covalent ligand binding to nucleic acids: Present and future

“…From this one can make a physically senseless conclusion about that the given physical fac tor does not give a contribution into stabilization of the investigated complexes (see discussion of the problem in work [5]). On the contrary, by a series of authors it has been shown that only the members of decomposi tion not formed by compensation of various interac tions may correlate with charge/structural properties of a ligand and with experimental energy of complex formation (ΔG exp ) [11,12]. Consequently, energetic analysis of the process of complex formation in aque ous medium must operate just with the components of total Gibbs energy on the level of separate physical factors (van der Waals, electrostatic etc.…”

“…The cause of this is dual. Firstly, in a majority of cases the total energies do not demonstrate any correlation with the properties of the very ligand (for example, with charge and type/ramification of side groups [12]) and are there fore useless for interpretation of binding energetics and also during solving problems of QSAR type (directed modification of ligand with an aim of opti mization of its medicobiological effect). Secondly, in consequence of the compensational effect the value of total energy of each separately taken physical factor may be close to zero (for example, ΔG VDW ≈ 0 for inter calators [5] and ΔG EL ≈ 0 for DNA minor groove bind…”

“…The most complete decomposition of Gibbs free energy into energetic members used by various authors (see works [4,5,8,10] and references therein) may be presented in the form of equation (1): (1) where ΔG total denotes the sum of theoretically calcu lated energetic terms; ΔG conf [2,5,10,11] -energetic contribution from conformational changes in mole cules upon complex formation; ΔG VDW [5,8,11], ΔG EL [11,12] and ΔG HYD [5] -contributions from van der Waals, electrostatic and hydrophobic interactions; ΔG CT [5,13] -contribution from interactions condi tioned by "charge transfer"; ΔG PE [1][2][3] -polyelec trolytic contribution; ΔG HB [5] -sum contribution from the energetics of loss of hydrogen bonds «to water» and formation of new intermolecular H bonds in complex; ΔG entr [14,15] -entropic contribution conditioned by the change of the total number of degrees of freedom of the system (translational, rota tional and vibrational) and also change of NA stiffness upon complex formation. Terms ΔG VDW , ΔG EL and ΔG HB further expand into interaction with aqueous medium and interaction of molecules in complex (in vacuo).…”

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

“…Hence, the 10-mer oligonucleotide duplex, d(CGCTCGAGCG) 2 , was used as the model DNA receptor. It was shown that such length of DNA is long enough for correct reproducing of electrostatic interaction for the group of aromatic intercalators [122].…”

Dimerization Energetics of DNA Minor Groove Binders

“…The corresponding values of el qualitatively agree with the values Δ im el > 0 quoted in Table 1. At the same time, an increase of the charge density at the center of a complex near two negative poles of dimers results in an energy-favorable interaction with the aqueous environment, Δ solv el < 0, owing to the polarization of the latter (Table 1); this effect is well-known for the binding of charged molecules-intercalators with DNA [35].…”