Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins

Area of Science:

• Protein structure analysis
• Biophysics
• Computational biology

Background:

• Amphipathic alpha-helices exhibit periodic hydrophobicity variations.
• The choice of hydrophobicity scale impacts the detection of this periodicity.

Purpose of the Study:

• To compare 38 hydrophobicity scales for identifying alpha-helix periodicity.
• To compute an optimal scale using a novel eigenvector method.
• To refine the understanding of alpha-helix structure and amphipathicity.

Main Methods:

• Comparison of 38 hydrophobicity scales.
• Application of a new eigenvector method for scale optimization.
• Analysis using discrete Fourier transform and least-squares harmonic fit.
• Calculation of the alpha amphipathic index.

Main Results:

• An optimized hydrophobicity scale was computed, maximizing the alpha amphipathic index.
• The least-squares method provides more reliable period estimation for shorter sequences.
• Approximately 50% of alpha-helices appear amphipathic.
• Helices are slightly more open (3.7 residues/turn) than the canonical 3.6.
• Arginine demonstrates unexpected hydrophobic behavior in amphipathic helices.

Conclusions:

• The optimized scale accurately predicts alpha-amphipathicity and correlates well with existing scales.
• The study refines the structural parameters of alpha-helices, particularly their openness.
• The unexpected hydrophobic nature of arginine in amphipathic helices warrants further investigation.