Specificity in the interaction of non intercalative groove binding ligands with nucleic acids.
Date
1985-08
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Abstract
This paper presents results of theoretical computations on the interaction energies
and geometries for the binding to nucleic acids of a number of representative groove binding
non intercalating drugs: netropsin, distamycin A, SN 18071, etc. The computations account for
the specificity of binding in all cases and demonstrate that the formation of hydrogen bonds is
not necessary neither for binding nor for the preference for the minor groove of AT sequences
of B-DNA. It appears that if a relatively good steric fit can be obtained in the minor groove, the
interaction will be preferentially stabilized there by the favorable electrostatic potential
generated in this groove by the AT sequences.
The computation of the interaction energies in free space does not reproduce, however, the
order of affinities of the ligands studied and yields too great values of the binding energies. The
introduction of the solvent effect, through the computation of the hydration and cavitation
effects, confirms the specificity, improves the ordering and brings the values of the energies
close to the experimental ones.
The theoretical account of the "surprising" effect of netrospin binding to the major groove
of the TψC stem of tRNAPhe confirms the decisive significance of the distribution of the
molecular electrostatic potential for the selection of the binding site. The inclusion in the
computations of the flexibility of DNA enables to predict correctly the main features of
the macromolecular deformation upon the binding of the ligand.
Description
Keywords
Groove ligands, non intercalative, molecular electrostatic potential, solvent, flexibility
Citation
Pullman B. Specificity in the interaction of non intercalative groove binding ligands with nucleic acids. Journal of Biosciences. 1985 Aug; 8(3&4): 681-688.