Conservation of amphipathic conformations in multiple protein structural alignments.

Protein amphipathic conformations, mainly alpha-helices and beta-strands, are believed to play an important role in protein folding, stability and function. The most popular method for characterizing such structures is the hydrophobic moment. We have analyzed the distribution of hydrophobic moment characteristics (peak magnitude, amphipathic indices and characteristic frequency) in a data bank containing several families of distant sequences multiply aligned by structural superposition. Sequence fragments were classified according to alpha-helix, beta-strand, non-alpha and non-beta conformations. This data bank provided an enhanced sample space compared with those previously reported in the literature. Precautions were taken to reduce over-representation of homologous sequences. Approximately 50% of all individual alpha-helices showed a hydrophobic moment peak in the expected position of the periodicity spectrum while only 38% of individual beta-strands fell in the expected range. False positives account for a surprisingly large 14 and 36% of the non-alpha and non-beta samples respectively. Conservation of hydrophobic moment characteristics and mainly the hydrophobic peak position in the expected periodicity range was examined in the multiple alignments of the distant sequences. Helices tend to conserve more frequently their hydrophobic moment than any other conformation and yet only 13% of all helical segments display such conservation in three-quarters or more of the familial sequences; the similar observation for beta-strands was even lower at 9%. Nonetheless, strongly hydrophobic positions within the structural segments were more conserved than expected.