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.

Key words: molecular modeling, intercalation, specificity recognition, B-DNA, mitoxantrone