Essential Amino Acids Hydrophobicity Scales – see hyd.xls

–Oxford Journals

Several hydrophobicity scales have been published for various uses. Some of them are presented in Table 1.

  1. Kyte-Doolittle scale [Kyte and Doolittle, 1982][1]:
  2. used for detecting hydrophobic regions in proteins. Regions with a positive value are hydrophobic.
  3. can be used for identifying both surface-exposed regions as well as transmembrane regions. Short window sizes of 5-7 generally works well for predicting putative surface-exposed regions. Large window sizes of 19-21 is well suited for finding transmembrane domains if the values calculated are above 1.6.
  4. Engelman scale[Engelman et al., 1986][2]:
  5. also known as the GES-scale
  6. can be used for prediction of protein hydrophobicity
  7. useful for prediction transmembrane regions in proteins.
  8. Eisenberg scale[Eisenberg et al., 1984][3]:
  9. a normalized consensus hydrophobicity scale
  10. Hopp-Woods scale [Hopp and Woods, 1983][4]:
  11. developed for identification of potential antigenic sites in proteins
  12. is a hydrophilic index where apolar residues have been assigned negative values. Antigenic sites are likely to be predicted when using a window size of 7
  13. Cornette scale[Cornette et al., 1987][5]:
  14. an optimal hydrophobicity scale based on 28 published scales
  15. suitable for prediction of alpha-helices in proteins.
  16. Rose scale[Rose et al., 1985][6]:
  17. a scale correlated to the average area of buried amino acids in globular proteins
  18. is a scale which is showing the surface accessibility of a protein
  19. Janin scale[Janin, 1979][7]:
  20. based on the accessible and buried amino acid residues of globular proteins.
  21. Wimley-White scale [Wimley and White, 1996][8]:
  22. Hessa et al. scale [Hessa et al, 2005][9]:
  23. Bumble scale [Bumble, 1999][10]:
  24. Wolfenden et al [Wolfenden, 1981][11]:
  25. Sweet-Eisenberg [Sweet & Eisenberg., 1983][12]:
  26. Abraham-Leo[13]
  27. Bull & Breese[14]
  28. Guy[15]
  29. Miyazawa et al.[16]
  30. Roseman[17]
  31. Welling & al[18]
  32. Parker & al[19]: HPLC
  33. Cowan[20]: HPLC pH = 7.5
  34. Manavalan et al.[21]:Average surrounding hydrophobicity
  35. Black[22]:Hydrophobicity of physiological L-alpha amino acids
  36. Fauchere et al.[23]:Hydrophobicity scale (pi-r).
  37. Rao & Argos[24]: Membrane buried helix parameter
  38. Wilsonet al[25]: Hydrophobic constants derived from HPLC peptide retention times
  39. Cowan-Whittaker[26]: Hydrophobicity indices at ph 3.4 determined by HPLC

TABLE I Distribution Coefficients of the 19 Amino Acid Side Chains

Amino acid / RH (side chain) / v>wa / c>wb / VHc / CHd / GUe / WWf / WWthg
Least polar
ILE / n-butane / 2.15 / 4.92 / –0.60 / 0.24 / 2.04 / 2.16 / –1.12
LEU / isobutane / 2.28 / 4.92 / –0.55 / –0.02 / 1.76 / 2.29 / –1.25
PHE / toluene / –0.76 / 2.98 / –0.32 / 0.00 / 2.09 / 2.68 / –1.71
VAL / propane / 1.99 / 4.04 / –0.31 / 0.09 / 1.18 / 1.61 / –0.46
CYS / methanethiol / –1.24 / 1.28 / –0.13 / 0.00 / ND / 1.23 / –0.02
MET / methylethylsulfide / –1.48 / 2.35 / –0.10 / –0.24 / 1.32 / 1.71 / –0.67
ALA / methane / 1.94 / 1.81 / 0.13 / –0.29 / 0.52 / 0.87 / 0.50
TRP / 3-methylindole / –5.88 / 2.33 / 0.30 / –0.59 / 2.51 / 2.96 / –2.09
THR / ethanol / –4.88 / –2.57 / 0.52 / –0.71 / 0.27 / 0.95 / 0.25
TYR / 4-methylphenol / –6.11 / –0.14 / 0.68 / –1.02 / 1.63 / 1.67 / –0.71
GLY / hydrogen / 2.39 / 0.94 / 0.74 / –0.34 / 0.00 / 1.01 / 1.15
SER / methanol / –5.06 / –3.40 / 0.84 / –0.75 / 0.04 / 0.85 / 0.46
ASN / acetamide / –9.68 / –6.64 / 2.05 / –1.18 / –0.01 / 0.30 / 0.85
HIS / 4-methylimidazole / –10.27 / –4.66 / 2.06 / –0.94 / 0.95 / 0.92 / 2.33
GLN / propionamide / –9.38 / –5.54 / 2.36 / –1.53 / –0.07 / 0.30 / 0.77
ARG / N-propylguanidine / –19.92 / –14.92 / 2.58 / –2.71 / –1.32 / 2.99 / 1.81
GLU / propionic acid / –10.24 / –6.81 / 2.68 / –0.90 / –0.79 / –2.53 / 3.63
LYS / n-butylamine / –9.52 / –5.55 / 2.71 / –2.05 / 0.08 / 2.49 / 2.80
ASP / acetic acid / –10.95 / –8.72 / 3.49 / –1.02 / ND / –2.46 / 3.64
Most polar
r2 versus VHh / 0.73 / 0.83 / (1.0) / 0.66 / 0.59 / 0.30 / 0.77
r2 versus CHh / 0.82 / 0.80 / 0.66 / (1.0) / 0.48 / 0.00 / 0.35
p versus VHi / 0.000001 / <0.0000001 / 0.00003 / 0.003

Distribution coefficients of the 19 amino acid side chains (RH) at pH 7, expressed in kcal/mol at 25°C, sorted according to their decreasing tendencies (VH) to be found in a transmembrane helix (Hessa et al., 2005). Experimental scales are shown in bold, theoretical scale in normal type.

a Side-chain Kd values for side-chain transfer from vapor to water (Wolfenden et al., 1981).

b Side-chain Kd values for transfer from cyclohexane to water (Radzicka and Wolfenden, 1988).

c Tendency of amino acid residue to be found in a transmembrane helix (Hessa et al., 2005).

d Tendency of amino acid residue to be buried in the interior of a globular protein (Chothia, 1976).

e Amino acid side-chain Kd values for transfer from wet octanol to water (Guy, 1985).

f Pentapeptide Kd values for transfer from water to wet octanol (Wimley et al., 1996).

g Theoretical pentapeptide Kd values for transfer from water to wet octanol, after adjustment for the estimated effects of occlusion by neighboring residues (Wimley et al., 1996, Table II, column 3).

h Value of the correlation coefficient (r) obtained by linear regression of distribution coefficients against the VH or the CH scales.

i Probability that this experimental scale is not related to the VH scale, i.e., that the null hypothesis is true.

[1] Kyte J, Doolittle RF. A Simple Method for Displaying the Hydropathic Character of a Protein. J Mol Biol 1982;157:105-132.

[2] Engelman DM, Steitz TA, Goldman A. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu Rev Biophys Biophys Chem 1986;15:321-353.

[3] Eisenberg D, Schwarz E, Komaromy M, Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol 1984;179:125-142.

[4] Hoop TP, Woods KR. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA 1981;78:3824-3828.

[5] Cornette JL, Cease KB, Margalit H, Spouge JL, Berzofsky JA, DeLisi C. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J Mol Biol 1987;195:659-685.

[6] Rose GD, Geselowitz AR, Lesser GJ, Lee RH, Zehfus MH. Hydrophobicity of amino acid residues in globular proteins. Science 1985;229:834-838.

[7] Janin J. Surface and inside volumes in globular proteins. Nature 1979;277:491-492.

[8] Wimley WC, White SH, Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nature Struct Biol 1996;3:842-848.

[9] Hessa T, Kim H, Bihlmaier K, Lundin C, Boekel J, Andersson H, Nilsson I, White SH, von Heijne G. Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 2005;433:377-381, supplementary data.

[10]Bumble S. The Design of Life: Information Technology, “Knapsack” and “Synprops” Used to Engineer the Sequence of Amino Acid Residues in Proteins [online] [cited June 1, 2007]. & Bumble S. Computer Generated Physical Properties, CRC Press, LLC, Boca Raton, 1999

[11] Wolfenden R, Andersson L, Cullis P, SouthgateC. Affinities of Amino Acid Side Chains for Solvent Water. Biochemistry 1981;20:849-855.

[12] Sweet RM, Eisenberg D. Correlation of sequence hydrophobicities measures similarity in three-dimensional protein structure. J Mol Biol 1983;171:479-488.

[13] Abraham D.J., Leo A.J. Extension of the fragment method to calculate amino acid zwitterions and side chain partition coefficients. Proteins 1987;2:130-152.

[14] Bull HB, Breese K. Surface tension of amino acid solutions: A hydrophobicity scale of the amino acid residues. Arch Biochem Biophys 1974;161:665-670.

[15] Guy HR. Amino acid side-chain partition energies and distribution of residues in soluble proteins. Biophys J 1985;47:61-70.

[16] Miyazawa S, Jernigen RL. Estimation of Effective Interresidue Contact Energies from Protein Crystal Structures: Quasi-Chemical Approximation. Macromolecules 1985;18:534-552.

[17] Roseman MA. Hydrophilicity of polar amino acid side-chains is markedly reduced by flanking peptide bonds. J Mol Biol 1988;200:513-522.

[18] Welling GW, Weijer WJ, Van der Zee R, Welling-Wester S. Prediction of sequential antigenic regions in proteins. FEBS Lett 1985;188:215-218.

[19] Parker JMR, Guo D, Hodges RS. New Hydrophilicity Scale Derived from High-Performance Liquid Chromatography Peptide Retention Data: Correlation of Predicted Surface Residues with Antigenicity and X-ray-Derived Accessible Sites? Biochemistry 1986;25:5425-5431.

[20] Cowan R., Whittaker R.G. Hydrophobicity indices for amino acid residues asdetermined by HPLC. Peptide Research 1990;3:75-80.

[21] Manavalan P, Ponnuswamy PK. Hydrophobic character of amino acid residues in globular proteins. Nature 1978;275:673-674.

[22] Black SD, Mould DR. Development of Hydrophobicity Parameters to Analyze Proteins Which Bear Post- or Cotranslational Modifications. Anal Biochem 1991;193:72-82. Available online: URL:

[23] Fauchere J-L, Pliska VE. Hydrophobic parameters of amino-acid side-chains from the partitioning of N-acetyl-amino-acid amide. Eur J Med Chem 1983;18:369-375.

[24] Rao MJK, Argos P. A conformational preference parameter to predict helices in integral membrane proteins. Biochim Biophys Acta 1986;869:197-214.

[25] Wilson KJ, Honegger A, Stotzel RP, Hughes GJ. The behaviour of peptides on reverse-phase supports during high-pressure liquid chromatography. Biochem J 1981;199:31-41.

[26] Cowan R, Whittaker RG. Hydrophobicity indices for amino acid residues asdetermined by HPLC. Peptide Research 1990;3:75-80.