title: 50 years of amino acid hydrophobicity scales: revisiting the capacity for peptide classification.
abstract: BACKGROUND
  Physicochemical properties are frequently analyzed to characterize protein-sequences of known and unknown function. Especially the hydrophobicity of amino acids is often used for structural prediction or for the detection of membrane associated or embedded β-sheets and α-helices. For this purpose many scales classifying amino acids according to their physicochemical properties have been defined over the past decades. In parallel, several hydrophobicity parameters have been defined for calculation of peptide properties. We analyzed the performance of separating sequence pools using 98 hydrophobicity scales and five different hydrophobicity parameters, namely the overall hydrophobicity, the hydrophobic moment for detection of the α-helical and β-sheet membrane segments, the alternating hydrophobicity and the exact ß-strand score.
  
  
  RESULTS
  Most of the scales are capable of discriminating between transmembrane α-helices and transmembrane β-sheets, but assignment of peptides to pools of soluble peptides of different secondary structures is not achieved at the same quality. The separation capacity as measure of the discrimination between different structural elements is best by using the five different hydrophobicity parameters, but addition of the alternating hydrophobicity does not provide a large benefit. An in silico evolutionary approach shows that scales have limitation in separation capacity with a maximal threshold of 0.6 in general. We observed that scales derived from the evolutionary approach performed best in separating the different peptide pools when values for arginine and tyrosine were largely distinct from the value of glutamate. Finally, the separation of secondary structure pools via hydrophobicity can be supported by specific detectable patterns of four amino acids.
  
  
  CONCLUSIONS
  It could be assumed that the quality of separation capacity of a certain scale depends on the spacing of the hydrophobicity value of certain amino acids. Irrespective of the wealth of hydrophobicity scales a scale separating all different kinds of secondary structures or between soluble and transmembrane peptides does not exist reflecting that properties other than hydrophobicity affect secondary structure formation as well. Nevertheless, application of hydrophobicity scales allows distinguishing between peptides with transmembrane α-helices and β-sheets. Furthermore, the overall separation capacity score of 0.6 using different hydrophobicity parameters could be assisted by pattern search on the protein sequence level for specific peptides with a length of four amino acids.
authors.affiliation: Department of Biosciences, Molecular Cell Biology of Plants, Goethe University, Max von Laue Str. 9, 60438, Frankfurt/Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Simm
authors.affiliation: Molecular Bioinformatics, Cluster of Excellence Frankfurt "Macromolecular Complexes", Institute of Computer Science, Faculty of Computer Science and Mathematics, Goethe-University Frankfurt, Robert-Mayer-Str. 11-15, 60325, Frankfurt/Main, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Einloft
authors.affiliation: Department of Biosciences, Molecular Cell Biology of Plants, Goethe University, Max von Laue Str. 9, 60438, Frankfurt/Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mirus
authors.affiliation: Department of Biosciences, Molecular Cell Biology of Plants, Cluster of Excellence Frankfurt (CEF) and Buchmann Institute of Molecular Life Sciences (BMLS), Goethe University, Max von Laue Str. 9, 60438, Frankfurt/Main, Germany. schleiff@bio.uni-frankfurt.de.
authors.forename: Enrico
authors.initials: E
authors.lastname: Schleiff
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000145:classification; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D011237:Predictive Value of Tests; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D012016:Reference Values; D015203:Reproducibility of Results; D013997:Time Factors; D014894:Weights and Measures
chemical_list: D000596:Amino Acids; D008565:Membrane Proteins
keywords: Alternate hydrophobicity; Amino acid pattern; Beta-sheet; Hydrophobicity scale; Transmembrane helix; Transmembrane sheets