title: Modelling repressor proteins docking to DNA.
abstract: The docking of repressor proteins to DNA starting from the unbound protein and model-built DNA coordinates is modeled computationally. The approach was evaluated on eight repressor/DNA complexes that employed different modes for protein/ DNA recognition. The global search is based on a protein-protein docking algorithm that evaluates shape and electrostatic complementarity, which was modified to consider the importance of electrostatic features in DNA-protein recognition. Complexes were then ranked by an empirical score for the observed amino acid /nucleotide pairings (i.e., protein-DNA pair potentials) derived from a database of 20 protein/ DNA complexes. A good prediction had at least 65% of the correct contacts modeled. This approach was able to identify a good solution at rank four or better for three out of the eight complexes. Predicted complexes were filtered by a distance constraint based on experimental data defining the DNA footprint. This improved coverage to four out of eight complexes having a good model at rank four or better. The additional use of amino acid mutagenesis and phylogenetic data defining residues on the repressor resulted in between 2 and 27 models that would have to be examined to find a good solution for seven of the eight test systems. This study shows that starting with unbound coordinates one can predict three-dimensional models for protein/DNA complexes that do not involve gross conformational changes on association.
authors.affiliation: Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Aloy
authors.forename: G
authors.initials: G
authors.lastname: Moont
authors.forename: H A
authors.initials: HA
authors.lastname: Gabb
authors.forename: E
authors.initials: E
authors.lastname: Querol
authors.forename: F X
authors.initials: FX
authors.lastname: Aviles
authors.forename: M J
authors.initials: MJ
authors.lastname: Sternberg
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016208:Databases, Factual; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000378:metabolism*; D055672:Static Electricity; D013223:Statistics as Topic
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins