The DNA-binding ability of the zinc-finger (ZF) protein and the modulation of its affinity to DNA through amino acid mutations were theoretically investigated. Classical molecular dynamics and energy decomposition analysis based on large-scale ab mitio fragment molecular orbital calculations were Used to obtain the DNA binding affinities: of wild type and three: mutant ZFs. Calculated bin ding :free energies qualitatively well explained the DNA binding affinity modulation experimentally observed by Dhanasekaran et al. [Dhamisekaran, M.; et;al., Biochemistry 2007, 46, 7506-7513]. It had been considered that only the alpha-helix domain in the ZF plays an important role in DNA recognition; however, our results clearly show that the N-terminal regions, BR.1 and BR2, also play important roles in DNA recognition.