Hydrophobicity Scale and Transfer Free Energy Calculator
Find the Kyte-Doolittle hydropathy index and Fauchère-Pliska transfer free energy for any amino acid, or a full sequence, residue by residue.
💧 What is the Hydrophobicity Scale and Transfer Free Energy Calculator?
The hydrophobicity scale and transfer free energy calculator looks up two standard amino acid hydrophobicity measures for every residue in a sequence you type: the Kyte-Doolittle hydropathy index (a unitless empirical scale) and the Fauchère-Pliska octanol-water transfer free energy (a real thermodynamic quantity in kcal/mol). It reports the sum and per-residue average for both scales, plus a full residue-by-residue breakdown table.
Structural biology and biochemistry courses use hydrophobicity scales to teach how amino acid side chain chemistry predicts protein structure, particularly which residues cluster in a folded protein's hydrophobic core versus its solvent-exposed surface. Membrane biology and bioinformatics use the Kyte-Doolittle scale specifically to scan protein sequences for likely transmembrane helices, since a run of consistently hydrophobic residues about 20 amino acids long is the classic signature of a membrane-spanning segment. Protein engineers and drug designers use Fauchère-Pliska-style transfer free energies to estimate how a point mutation changes a protein's stability or a peptide's membrane permeability.
A common misconception is that all hydrophobicity scales rank amino acids identically. They do not, different scales were built from different experiments (vapor-to-water transfer, octanol-water partitioning, side-chain burial statistics) and can disagree noticeably for individual residues, tryptophan is the textbook example, ranking near the most hydrophobic on Fauchère-Pliska but negative on Kyte-Doolittle. Comparing values across scales without checking which scale a source used is a common source of confusion.
This calculator removes the need to manually look up 20 different residue values from a table and add them by hand, letting students and researchers immediately see both scales side by side for any sequence, single residue or full peptide, they are interested in.
📐 Formula
📖 How to Use This Calculator
Steps
💡 Example Calculations
Example 1 — Single Residue: Tryptophan
Sequence: "W" (a single tryptophan residue)
Example 2 — Hydrophobic Transmembrane-Like Segment
Sequence: "LLLIVL" (4 leucine, 1 isoleucine, 1 valine, a typical hydrophobic stretch)
Example 3 — Hydrophilic, Charged Segment
Sequence: "DEKR" (aspartate, glutamate, lysine, arginine, all charged residues)
❓ Frequently Asked Questions
🔗 Related Calculators
What does the Hydrophobicity Scale and Transfer Free Energy Calculator do?
It looks up two standard hydrophobicity values, the Kyte-Doolittle hydropathy index and the Fauchère-Pliska octanol-water transfer free energy, for every residue in a typed amino acid sequence, then reports the sum and per-residue average for both scales along with a full residue-by-residue table.
What is the Kyte-Doolittle scale?
The Kyte-Doolittle scale is a widely used, unitless hydropathy index for the 20 standard amino acids, published in 1982, originally designed to identify hydrophobic transmembrane segments in protein sequences by scanning for stretches of consistently high positive scores.
What is the Fauchère-Pliska scale?
The Fauchère-Pliska scale reports each amino acid side chain's octanol-water transfer free energy in kcal/mol, a real thermodynamic quantity measured from partitioning experiments. Positive values mean the side chain favors the nonpolar octanol phase (hydrophobic); negative values mean it favors the polar water phase (hydrophilic).
Which amino acid is the most hydrophobic on the Fauchère-Pliska scale?
Tryptophan (Trp, W) has the highest Fauchère-Pliska value at 1.85 kcal/mol, followed closely by isoleucine (1.80) and phenylalanine (1.79). All three have large, nonpolar side chains that strongly favor partitioning into a nonpolar environment.
Which amino acid is the most hydrophilic?
Arginine (Arg, R) has the most negative Fauchère-Pliska value at -1.01 kcal/mol and one of the most negative Kyte-Doolittle scores at -4.5, both reflecting its long, positively charged, highly polar side chain, which strongly favors water over a nonpolar environment.
Why do Kyte-Doolittle and Fauchère-Pliska sometimes disagree on the same residue?
The two scales were built from different experimental and computational approaches, Kyte-Doolittle combines water-vapor transfer data with side-chain burial statistics, while Fauchère-Pliska is a direct octanol-water partition coefficient measurement. Tryptophan is the classic example, it ranks near the top on Fauchère-Pliska but scores negative on Kyte-Doolittle.
How is the average hydropathy of a sequence used in practice?
A sliding window average (commonly 19-20 residues wide) of the Kyte-Doolittle score along a protein sequence is the classic method for predicting transmembrane helices, a window average above roughly 1.6 to 2.0 signals a likely membrane-spanning segment. This calculator computes the average over the whole entered sequence, useful for comparing a candidate segment as a single unit.
Can I enter just one amino acid instead of a full sequence?
Yes, entering a single one-letter code (for example, just W) returns that single residue's Kyte-Doolittle and Fauchère-Pliska values directly, with sum and average both equal to that one residue's score.
What happens if I type an invalid character or a non-standard amino acid code?
Any character that is not one of the 20 standard one-letter amino acid codes (spaces, numbers, punctuation, or codes for nonstandard residues) is simply skipped and does not count toward the sum, average, or residue count, the calculator reports how many characters were ignored.
What units does the Fauchère-Pliska result use?
Fauchère-Pliska transfer free energy values are reported in kilocalories per mole (kcal/mol), the actual thermodynamic unit from the original octanol-water partitioning experiments. The Kyte-Doolittle hydropathy index, in contrast, is a unitless empirical scale and has no physical units.