title: Modeling helix-turn-helix protein-induced DNA bending with knowledge-based distance restraints.
abstract: A crucial element of many gene functions is protein-induced DNA bending. Computer-generated models of such bending have generally been derived by using a presumed bending angle for DNA. Here we describe a knowledge-based docking strategy for modeling the structure of bent DNA recognized by a major groove-inserting alpha-helix of proteins with a helix-turn-helix (HTH) motif. The method encompasses a series of molecular mechanics and dynamics simulations and incorporates two experimentally derived distance restraints: one between the recognition helix and DNA, the other between respective sites of protein and DNA involved in chemical modification-enabled nuclease scissions. During simulation, a DNA initially placed at a distance was "steered" by these restraints to dock with the binding protein and bends. Three prototype systems of dimerized HTH DNA binding were examined: the catabolite gene activator protein (CAP), the phage 434 repressor (Rep), and the factor for inversion stimulation (Fis). For CAP-DNA and Rep-DNA, the root mean square differences between model and x-ray structures in nonhydrogen atoms of the DNA core domain were 2.5 A and 1.6 A, respectively. An experimental structure of Fis-DNA is not yet available, but the predicted asymmetrical bending and the bending angle agree with results from a recent biochemical analysis.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, ROC.
authors.forename: W S
authors.initials: WS
authors.lastname: Tzou
authors.forename: M J
authors.initials: MJ
authors.lastname: Hwang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019077:Helix-Turn-Helix Motifs; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D004247:DNA