Mazerski J, Martelli S, Borowski E
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Acta Biochim Pol. 1998;45(1):1-11.
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.
采用GROMOS 87力场，通过在水中进行分子动力学模拟，研究了抗肿瘤药物氨甲蒽醌和米托蒽醌与十二聚体双链d(CGCGAGCTCGCG)2的嵌入结合。通过短时间的预模拟测试了许多合理的结合取向。结果表明，在能量有利的取向下，蒽醌发色团垂直于碱基间氢键的方向。药物的螺旋状侧链适合于小沟。预模拟中获得的最佳取向应用于主要模拟。发现两种药物与十二聚体双链的嵌入复合物结构之间存在微小但显著的差异，米托蒽醌复合物具有更有利的能量。讨论了造成这些差异的相互作用的分子性质。
