title: Identifying DNA-binding proteins using structural motifs and the electrostatic potential.
abstract: Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix-turn-helix (HTH), helix-hairpin-helix (HhH) and helix-loop-helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif.
authors.affiliation: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Hugh.Shanahan@physics.org
authors.forename: Hugh P
authors.initials: HP
authors.lastname: Shanahan
authors.forename: Mario A
authors.initials: MA
authors.lastname: Garcia
authors.forename: Susan
authors.initials: S
authors.lastname: Jones
authors.forename: Janet M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D023281:Genomics; D018257:Helix-Loop-Helix Motifs; D019077:Helix-Turn-Helix Motifs; D008958:Models, Molecular; D055672:Static Electricity
chemical_list: D004268:DNA-Binding Proteins