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The effect of drug‐DNA interactions on the intercalation site formation
Author(s) -
Miroshnychenko K. V.,
Shestopalova A. V.
Publication year - 2010
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.22290
Subject(s) - intercalation (chemistry) , dna , chemistry , stereochemistry , docking (animal) , crystallography , a dna , biochemistry , inorganic chemistry , medicine , nursing
The problem of intercalation site formation in the undistorted B‐DNA of different length and sequence was considered. Three models of DNA intercalation targets were proposed that accounted for the binding features of intercalators ethidium, daunomycin and 9‐amino[ N ‐(2‐dimethylamino)ethyl]‐acridine‐4‐carboxamide (9‐amino‐DACA). The automated docking of ligands into the constructed DNA‐targets produced correct structures of complexes for ethidium and daunomycin when asymmetrically unwound DNA was used as target. To obtain the correct structure of 9‐amino‐DACA‐DNA complex, the manual docking was applied. The results of docking of ligands into different DNA‐targets indicate that, upon formation of the intercalation target, it is sufficient to take into account only the most significant unwinding in one particular helical step: in the intercalation step (for ethidium and 9‐amino‐DACA) or in the adjacent helical step (for daunomycin). The unwinding or overwinding of subsequent helical steps could be refined later during the optimization of the obtained intercalation complex. The unwinding of the DNA helical step on the large angle produces the 5′‐North/3′‐South asymmetry of sugar conformations in this step. The value of the total unwinding of the DNA in the intercalation complex was found to be dependent on the sequence and length of the DNA‐target. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010