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- RE: The hydrophobic moment: an early bioinformatics method and de novo protein design
In their recent Science report, David Baker and co-workers (1) investigate and discuss the principles for designing de novo proteins with cavities formed by curved β-sheets. The structures of nine de novo protein models, experimentally verified by NMR spectroscopy or x-ray crystallography, confirmed the existence of five different folding types (from A to E) (1). We have re-analyzed those five designs using the virtual spectroscopy based on the hydrophobic moment measurement (normalized PRIFT method and least-squares procedure) (2–4).
The frequency axes of the periodograms were divided into three equally spaced zones: X (0-0.166), Y (0.167-0.333) and Z (0.334-0.500) (3, 4). The box-and-whisker rule was used to detect outliers and extremes, i.e., dominant peaks.
The results show distinct periodicity patterns typical of each folding type. Folds A (4R80) and C (5TS4) are characterized by the dominant peaks in the regions XYZ of the periodogram, while fold B (5KPE) exhibits a dominant peak pattern within the XZ region. The third pattern XY is typical of the fold D (5L33), while the fourth pattern YZ characterizes the fold E (5TRV). Additionally, for the fold E the method is sensitive to the homodimer mutations with cavity based modifications, and results in the transformation of the basic YZ pattern into a new, XYZ one (5U35).Modular, Lego-like, construction principle based on α and β fold units (10) is typical of five examined folding types, with two ba...
Show MoreCompeting Interests: None declared.
