期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：26
页码：14819-14824
DOI：10.1073/pnas.251267298
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The amino acid sequence rules that specify {beta}-sheet structure in proteins remain obscure. A subclass of {beta}-sheet proteins, parallel {beta}-helices, represent a processive folding of the chain into an elongated topologically simpler fold than globular {beta}-sheets. In this paper, we present a computational approach that predicts the right-handed parallel {beta}-helix supersecondary structural motif in primary amino acid sequences by using {beta}-strand interactions learned from non-{beta}-helix structures. A program called BETAWRAP (http://theory.lcs.mit.edu/betawrap) implements this method and recognizes each of the seven known parallel {beta}-helix families, when trained on the known parallel {beta}-helices from outside that family. BETAWRAP identifies 2,448 sequences among 595,890 screened from the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/) nonredundant protein database as likely parallel {beta}-helices. It identifies surprisingly many bacterial and fungal protein sequences that play a role in human infectious disease; these include toxins, virulence factors, adhesins, and surface proteins of Chlamydia, Helicobacteria, Bordetella, Leishmania, Borrelia, Rickettsia, Neisseria, and Bacillus anthracis. Also unexpected was the rarity of the parallel {beta}-helix fold and its predicted sequences among higher eukaryotes. The computational method introduced here can be called a three-dimensional dynamic profile method because it generates interstrand pairwise correlations from a processive sequence wrap. Such methods may be applicable to recognizing other beta structures for which strand topology and profiles of residue accessibility are well conserved.
