title: Comprehensive analysis of sequences of a protein switch.
abstract: Switches form a special class of proteins that dramatically change their three-dimensional structures upon a small perturbation. One possible perturbation that we explore is that of a single point mutation. Building on the pioneering experimental work of Alexander et al. (Alexander et al. PNAS, 2007; 104,11963-11968) that determines switch sequences between α and α+β folds we conduct a comprehensive sequence sampling by a Markov Chain with multiple fitness criteria to identify new switches given the experimental folds. We screen for switch sequences using a combination of contact potential, secondary structure prediction, and finally molecular dynamics simulations. Statistical properties of switch sequences are discussed and illustrated to be most sensitive to mutation at the N- and C- termini of the switch protein. Based on this analysis, a particularly stable putative switch pair is identified and proposed for further experimental analysis.
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas.|Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas.
authors.forename: Szu-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.|Department of Electrical Engineering and Computing Systems, University of Cincinnati College of Medicine, Cincinnati, Ohio.|Department of Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, Ohio.|Department of Informatics, Nicholas Copernicus University, Torun, Poland.|Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Meller
authors.affiliation: Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas.|Department of Chemistry, University of Texas at Austin, Austin, Texas.
authors.forename: Ron
authors.initials: R
authors.lastname: Elber
mesh_terms: D000595:Amino Acid Sequence; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
keywords: contact maps; molecular dynamics; mutations; protein folds; secondary structure prediction; structural flips