The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Aβ(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, Aβ(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.
Zbilut, J. P., Colosimo, A., Conti, F., Colafranceschi, M., Manetti, C., Valerio, M. C., … Giuliani, A. (2003). Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and Aβ(1-40). Biophysical Journal, 85(6), 3544–3557. https://doi.org/10.1016/S0006-3495(03)74774-2