Deciphering protein sequence information through hydrophobic cluster analysis (HCA): current status and perspectives

Abstract

Ten years after the idea of hydrophobic cluster analysis (HCA) was conceived and first pub lished, theoretical and practical experience has shown this unconventional method of protein sequence anal ysis to be particularly efficient and sensitive, especially with families of sequences sharing low levels of se quence identity. This extreme sensitivity has made it possible to predict the functions of genes whose se quence similarities are hardly if at all detectable by current one-dimensional (1D) methods alone, and of fers a new way to explore the enormous amount of data generated by genome sequencing. HCA also pro vides original tools to understand fundamental fea tures of protein stability and folding. Since the last review of HCA published in 1990 [1], significant im provements have been made and several new facets have been addressed. Here we wish to update and summarize this information.