The Kyte-Doolittle scale assigns a hydrophobicity score to each amino acid. Using a sliding window, this plot reveals hydrophobic regions (membrane anchors, signal peptides) and hydrophilic surface-exposed regions.
Scores range from +4.5 (Ile, most hydrophobic) to −4.5 (Arg, most hydrophilic). Derived from transfer free energies of amino acid side chains between water and organic solvent, combined with interior burial frequencies in known protein structures.
The classic application of this plot. Segments with a mean score above 1.8 over a 19-residue window are very likely transmembrane α-helices — the window matches the ~20 residues needed to cross a lipid bilayer. This threshold appears as a dashed green line. GPCRs, ion channels, and transporters each show a characteristic number of peaks above 1.8. Switch to window size 19 to activate this prediction mode.
An amphipathic helix has one hydrophobic face and one hydrophilic face. On the plot, these appear as moderate oscillations rather than a sustained peak. Melittin is the textbook example — its N-terminal region lies parallel to cell membranes, inserting one hydrophobic face into the bilayer. Most antimicrobial peptides (cecropins, magainins, LL-37) are amphipathic helices; this geometry lets them disrupt bacterial membranes while sparing host cells.
Signal peptides are N-terminal sequences (15–30 residues) that direct proteins to the secretory pathway. On the plot they produce a sharp hydrophobic peak at the very start of the sequence — typically well above 1.8 — followed by a drop where the mature protein begins. Signal peptidase then cleaves this segment after translocation into the ER. Try the "Signal peptide" example above to see this pattern: the first ~20 residues are strongly hydrophobic, the remainder is mixed.