Hydrophobicity Profiles for Protein Sequence Analysis

Stanley R. Krystek1, William J. Metzler1, Jiri Novotny1

1 Bristol‐Myers Squibb Pharmaceutical Research Institute, Princeton
Publication Name:  Current Protocols in Protein Science
Unit Number:  Unit 2.2
DOI:  10.1002/0471140864.ps0202s00
Online Posting Date:  May, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Hydrophobic interactions are a major force in protein folding and numerous hydropathy scales have been developed to quantify the relative hydrophobicity of the amino acids. Hydropathy profiles can be used to examine the surface features of proteins in order to generate hypotheses that can be confirmed experimentally. This unit describes the application of hydrophobicity plots to typical problems and provides suggested uses for a few selected scales.

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Methodology
  • Applications
  • Conclusions
  • Accessibility of Software
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Anfinsen, C.B., Haber, E., Sela, M., and White, F.H., Jr. 1961. The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc. Natl. Acad. Sci. U.S.A. 47:1309‐1314.
   Argos, P., Rao, J.K.M., and Hargrave, P.A. 1982. Structural prediction of membrane‐bound proteins. Eur. J. Biochem. 128:565‐575.
   Atassi, M.Z. 1984. Antigenic structure of proteins. Eur. J. Biochem. 145:1‐20.
   Banghan, J.A. 1988. Data‐sieving hydrophobicity plots. Anal. Biochem. 174:142‐145.
   Barlow, D.J. and Thornton, J. 1988. Alpha helices in proteins. J. Mol. Biol. 210:601‐619.
   Bigelow, C.C. 1967. On the average hydrophobicity of proteins and the relation between it and protein structure. J. Theor. Biol. 16:187‐211.
   Biosym Technologies. 1991. Insight II/Homology Modules. Biosym Technologies, San Diego.
   Chothia, C. 1976. The nature of the accessible and buried surfaces of proteins. J. Mol. Biol. 105:1‐14.
   Cornette, J.L., Cease, K.B., Margalit, H., Spouge, J.L., Berzofsky, J.A., and DeLisa, C. 1987. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J. Mol. Biol. 195:659‐685.
   Eisenberg, D. 1984. Three‐dimensional structure of membrane and surface proteins. Annu. Rev. Biochem. 53:595‐623.
   Engleman, D.M., Steitz, T.A., and Goldman, A. 1986. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu. Rev. Biophys. Chem. 15:321‐353.
   Esposti, M.D., Crimi, M., and Venturoli, G. 1990. A critical evaluation of the hydropathy profile in membrane proteins. Eur. J. Biochem. 190:207‐219.
   Fauchere, J.L. and Pliska, V. 1983. Hydrophobic parameters P of amino acid side chains from the partitioning of N‐acetyl‐amino acid amides. Eur. J. Med. Chem. 18:369‐375.
   Fermi, G. 1975. Three‐dimensional Fourier synthesis of human deoxyhaemoglobin at 2.5 angstroms resolution, refinement of the atomic model. J. Mol. Biol. 97:237‐256.
   Finzel, B.C., Clancy, L.L., Holland, D.R., Muchmore, S.W., Watenpaugh, K.D., and Einspahr, H.M. 1989. Crystal structure of recombinant human interleukin‐1β at 2.0 angstroms resolution. J. Mol. Biol. 209:779‐791.
   Fraga, S. 1982. Theoretical prediction of protein antigenic determinants from amino acid sequences. Can. J. Chem. 60:2606‐2610.
   Genetics Computer Group. 1994. GCG Program Manual for the Wisconsin Package. Genetics Computer Group, Inc., Madison, Wis.
   Henderson, R., Baldwin, J.M., Ceska, T.A., Zemlin, F., Beckmann, E., and Downing, K.H. 1990. Model for the structure of bacteriorhodopsin based on high resolution electron cryomicroscopy. J. Mol. Biol. 213:899‐929.
   Hopp, T.P. 1984. Protein antigen conformation: Folding patterns and predictive algorithms; selection of antigenic and immunogenic peptides. Ann. Sclavo 2:47‐60.
   Hopp, T.P. 1989. Use of hydrophilicity plotting procedures to identify protein antigenic segments and other interaction sites. Methods Enzymol. 178:571‐585.
   Hopp, T.P. and Woods, K.R. 1981. Prediction of protein antigenic determinants from amino acid sequences. Proc. Natl. Acad. Sci.U.S.A. 78:3824‐3828.
   Janin, J. 1979. Surface and inside volumes in globular proteins. Nature 277:491‐492.
   Kauzmann, W. 1959. Some factors in the interpretation of protein denaturation. Adv. Prot. Chem. 14:1‐63.
   Krystek, S.R., Jr., Dias, J.A., Reichert, L.E., and Andersen, T.T. 1985a. Prediction of antigenic sites in follicle stimulating hormones: Difference profiles enhance antigenicity prediction methods. Endocrinology 117:1125‐1130.
   Krystek, S.R., Jr., Reichert, L.E., and Andersen, T.T. 1985b. Analysis of computer generated hydropathy profiles for human glycoprotein and lactogenic hormones. Endocrinology 117:1110‐1117.
   Krystek, S.R., Jr., Dias, J.A., and Andersen, T.T. 1991. Identification of subunit contact sites on the α‐subunit of lutropin. Biochemistry 30:1858‐1864.
   Krystek, S.R., Jr., Dias, J.A., and Andersen, T.T. 1992. Identification of a subunit contact site on the α‐subunit of follitropin. Pept. Res. 25:165‐168.
   Kuntz, I.D. 1972. Protein folding. J. Am. Chem. Soc. 94:4009‐4012.
   Kyte, J. and Doolittle, R.F. 1982. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157:105‐132.
   Landolt‐Marticorena, C., Williams, K.A., Deber, C.M., and Reithmeier, A.F. 1993. Nonrandom distribution of amino acids in the transmembrane segments of human type I single span membrane proteins. J. Mol. Biol. 229:602‐608.
   Levitt, M. 1976. A simplified representation of protein conformations for rapid simulation of protein folding. J. Mol. Biol. 104:59‐107.
   Nozaki, Y. and Tanford, C. 1971. The solubility of amino acids and two glycine peptides in aqueous ethanol and dioxane solutions. J. Biol. Chem. 246:2211‐2217.
   Parker, J.M.R., Guo, D., and Hodges, R.S. 1986. New hydrophobicity scale derived from high‐performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X‐ray‐derived accessible sites. Biochemistry 25:5425‐5432.
   Rao, J.K.M. and Argos, P. 1986. A conformational preference parameter to predict helices in integral membrane proteins. Biochim. Biophys. Acta 869:197‐214.
   Rose, G.D. and Dworkin, J.E. (1989). The hydrophobicity profile. In Prediction of Protein Structure and the Principles of Protein Conformation (G.D. Fasman, ed.) pp. 625‐633. Plenum, New York.
   Rose, G.D., Geselowitz, A.R., Lesser, G.J., Lee, R.H., and Zehfus, M.H. 1985. Hydrophobicity of amino acid residues in globular proteins. Science 229:834‐838.
   Roy, S. and Rose, G.D. 1980. Hydrophobic basis of packing in globular proteins. Proc. Natl. Acad. Sci. U.S.A. 8:4643‐4647.
   Tanaka, T., Slamon, D.J., and Cline, M.J. 1985. Efficient generation of antibodies to oncoproteins by using synthetic peptide antigens. Proc. Natl. Acad. Sci. U.S.A. 82:3400‐3404.
   Tanford, C. 1980. The Hydrophobic Effect. John Wiley & Sons, New York.
   von Heijne, G. and Blomberg, C. 1979. Transmembrane translocation of proteins. The direct transfer model. Eur. J. Biochem. 97:175‐181.
   Tripos Associates. 1993. Biopolymer/Composer Module. Tripos Associates, Inc., St. Louis, Mo.
   Wolfenden, R., Andersson, L., Cullis, P.M., and Southgate, C.C. 1981. Affinities of amino acid side chains for solvent water. Biochemistry 20:849‐855.
   Yoshioka, N. and Atassi, M.Z. 1986. Subunit interacting surfaces of human haemoglobin. Biochem. J. 234:457‐461.
Key References
   Engleman et al., 1986. See above.
  Provides applications of hydropathy profiles to transmembrane region prediction.
   Kyte and Doolittle, 1982. See above.
  Describes the fundamental development and application of hydropathy profiles.
PDF or HTML at Wiley Online Library