title: A theoretical study of the physicochemical mechanisms associated with DNA recognition modulation in artificial zinc-finger proteins.
abstract: 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 initio fragment molecular orbital calculations were used to obtain the DNA binding affinities of wild-type and three mutant ZFs. Calculated binding free energies qualitatively well explained the DNA binding affinity modulation experimentally observed by Dhanasekaran et al. [Dhanasekaran, M.; et al., Biochemistry 2007, 46, 7506-7513]. It had been considered that only the α-helix domain in the ZF plays an important role in DNA recognition; however, our results clearly show that the N-terminal regions, BR1 and BR2, also play important roles in DNA recognition.
authors.affiliation: Division of Advanced Sciences, Ocha-dai Academic Production, Ochanomizu University, Tokyo, Japan. mori.hirotoshi@ocha.ac.jp
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Mori
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueno-Noto
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA