We investigated the intercalation of an antitumor drug ellipticine into four adenine-thymine (AT) rich DNA duplexes with the focus on the configurational entropy, by means of molecular dynamics (MD) simulations. Two possible binding orientations of ellipticine in a DNA double helix were studied, and the orientation with the pyrrole nitrogen exposed into a major groove was identified as the more probable. The configurational entropy change of DNA is shown to contribute significantly to the binding free energy. The magnitude of this contribution depends on the exact DNA sequence. A detailed analysis revealed that the largest flexibility changes occurred in the sugar-phosphate backbone, resulting in an entropy gain in the most cases. The nucleobases were not involved in the changes of flexibility and entropy. BI/BII-like conformational transitions were observed after the intercalation of ellipticine, and the consequences of these transitions for the evaluation of entropy are discussed.