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Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Is Use of the Hydrophobic Moment a Sound Basis for Predicting the Structure-Function Relationships of Membrane Interactive α-Helices?

Author(s): David Phoenix and Frederick Harris

Volume 4, Issue 5, 2003

Page: [357 - 366] Pages: 10

DOI: 10.2174/1389203033487090

Price: $65


Amphiphilic α-helices play a fundamental role in protein - membrane association and show a segregation of polar and apolar amino acid residues. Based on correlations between amphiphilic properties and biological function, a number of theoretical approaches have been developed, which quantify α-helix amphiphilicity and then attempt to assign function. The most commonly used measure of amphiphilicity is the hydrophobic moment, < μH > , which, when used in conjunction with an α-helixs mean hydrophobicity, < H > , has been used to classify membrane interactive amphiphilic α- helices as either surface active or transmembrane. Here, the predictive efficacy of plot methodology is reviewed by examining published data, which compare the function of known membrane interactive amphiphilic α-helices to that assigned by this methodology. The results of this review are discussed in relation to the reliability of < μH > as a quantifier of α-helical amphiphilicity, and the ability of < μH > and < H > to describe α-helical structure / function relationships. It is concluded that hydrophobic moment plot methodology is not a generally reliable predictor of α-helical structure / function relationships. It appears that the inefficacy of plot methodology is primarily due to the inability of the plot diagram to accommodate the heterogeneity of the α-helical classes it attempts to define. However, the predictive efficacy of the methodology appears to be improved if other α-helical parameters are also considered when assigning α-helical function. It is suggested that the conventional methodology should be seen only as an indicator for the assignation of structure / function relationships, providing a guide to future experimental investigations.

Keywords: hydrophobic moment, amphiphilic, helical amphiphilicity

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