米托蒽醌与B-DNA相互作用的分子模拟

针对嵌插型抗癌药物米托蒽醌(mitoxantrone,MTX)同B-DNA间作用模式的争议,采用分子模拟方法研究了米托蒽醌分子与B-DNA分子的相互作用.结果表明:米托蒽醌分子插入到B-DNA中有大小沟选择性及碱基对特异性,更倾向从小沟方向插入到DNA分子中;对5'-CG碱基对有特异性识别.通过详细能量项的分析,揭示了米托蒽醌插入DNA分子的驱动力及对碱基的特异性识别作用主要是空间相互作用特别是静电相互作用.在最佳作用位点复合物的构象分析则表明蒽醌环只有一部分插入碱基对中,侧链在小沟中延磷酸基骨架以3'-5'方向伸展,并通过静电作用进一步增强米托蒽醌与B-DNA的结合.

Molecular Modeling of the Interaction Between Mitoxantrone and B-DNA

Molecular modeling methods have been applied to characterization of the intercalation mode of the anticancer drug mitoxantrone (MTX) into B-DNA fragments for controversies. The results show that there are groove selectivity and base pairs specificity recognition between MTX and B-DNA, MTX prefers to intercalate into DNA from the minor groove for the base pair 5 -CG. Through analyzing the detailed energy terms of DNA-MTX, the steric interactions, especially the electrostatic interactions were found to be the main factors to the primary drive of intercalation and base pairs specificity. The conformation of MTX-DNA at the best action site shows that only a portion of the chromophore of MTX was involved in the intercalation into DNA base pairs and the binding of MTX to DNA was potentially enhanced by the presence of side chains which could bind electrostatically to the phosphate groups spreading along 3 -5 of the B-DNA.