title: Predicting conformational switches in proteins.
abstract: We describe a new computational technique to predict conformationally switching elements in proteins from their amino acid sequences. The method, called ASP (Ambivalent Structure Predictor), analyzes results from a secondary structure prediction algorithm to identify regions of conformational ambivalence. ASP identifies ambivalent regions in 16 test protein sequences for which function involves substantial backbone rearrangements. In the test set, all sites previously described as conformational switches are correctly predicted to be structurally ambivalent regions. No such regions are predicted in three negative control protein sequences. ASP may be useful as a guide for experimental studies on protein function and motion in the absence of detailed three-dimensional structural data.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446, USA.
authors.forename: M
authors.initials: M
authors.lastname: Young
authors.forename: K
authors.initials: K
authors.lastname: Kirshenbaum
authors.forename: K A
authors.initials: KA
authors.lastname: Dill
authors.forename: S
authors.initials: S
authors.lastname: Highsmith
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000449:Aldehyde Reductase / Q000737:chemistry; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D020536:Enzyme Activators / Q000737:chemistry; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D008958:Models, Molecular; D009218:Myosins / Q000737:chemistry; D016328:NF-kappa B / Q000737:chemistry; D052002:NF-kappa B p50 Subunit; D010444:Peptide Elongation Factor Tu / Q000737:chemistry; D011328:Prions / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D045522:Recombinases; D015843:Serpins / Q000737:chemistry; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000737:chemistry; D015293:Transducin / Q000737:chemistry; D019895:Transposases
chemical_list: D004268:DNA-Binding Proteins; D020536:Enzyme Activators; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011328:Prions; D045522:Recombinases; D015843:Serpins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D000449:Aldehyde Reductase; D019895:Transposases; D010444:Peptide Elongation Factor Tu; D009218:Myosins; D019205:GTP-Binding Protein alpha Subunits, Gs; D015293:Transducin; D000262:Adenylyl Cyclases; D004264:DNA Topoisomerases, Type I