title: Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40).
abstract: The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Abeta(1-40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois, USA. joseph_p_zbilut@rush.edu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Zbilut
authors.forename: Alfredo
authors.initials: A
authors.lastname: Colosimo
authors.forename: Filippo
authors.initials: F
authors.lastname: Conti
authors.forename: Mauro
authors.initials: M
authors.lastname: Colafranceschi
authors.forename: Cesare
authors.initials: C
authors.lastname: Manetti
authors.forename: MariaCristina
authors.initials: M
authors.lastname: Valerio
authors.forename: Charles L
authors.initials: CL
authors.lastname: Webber
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D016000:Cluster Analysis; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012984:Software; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; D011108:Polymers; D011506:Proteins; D000097024:Acylphosphatase; C078592:amyloid beta-protein (1-40)