Open AccessThe geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations.
Author(s) -
Jan Mazerski,
Sante Martelli,
Edward Borowski
Publication year - 1998
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1998_4280
Subject(s) - dodecameric protein , molecular dynamics , mitoxantrone , intercalation (chemistry) , hydrogen bond , chemistry , chromophore , crystallography , anthraquinone , dna , base pair , computational chemistry , duplex (building) , stereochemistry , chemical physics , molecule , photochemistry , biology , biochemistry , inorganic chemistry , organic chemistry , chemotherapy , genetics
Intercalative binding of the antitumor drugs ametantrone and mitoxantrone to the dodecamer duplex d(CGCGAGCTCGCG)2 was studied by applying molecular dynamics in water with the GROMOS 87 force field. A number of reasonable binding orientations were tested by short pre-simulations. It was shown that in energetically favourable orientation the anthraquinone chromophore is perpendicular to the direction of inter-base hydrogen bonds. Helically shaped side-chains of the drugs fit to the minor groove. The best orientation obtained in pre-simulations was applied in the main simulations. Small but significant differences were found between structures of intercalation complexes of the two drugs with the dodecamer duplex, the mitoxantrone complex possessing more favourable energy. The molecular nature of interactions responsible for those differences has been discussed.