Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40)

Biophys J. 2003 Dec;85(6):3544-57. doi: 10.1016/S0006-3495(03)74774-2.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Anhydride Hydrolases / chemistry*
  • Acylphosphatase
  • Algorithms
  • Amyloid beta-Peptides / chemistry*
  • Biophysics / methods*
  • Cluster Analysis
  • Computer Simulation
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry*
  • Peptides / chemistry
  • Polymers / chemistry
  • Protein Binding
  • Protein Folding*
  • Protein Structure, Secondary
  • Proteins / chemistry
  • Software

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • Polymers
  • Proteins
  • amyloid beta-protein (1-40)
  • Acid Anhydride Hydrolases