Extracting information on folding from the amino acid sequence: accurate predictions for protein regions with preferred conformation in the absence of tertiary interactions.

TitleExtracting information on folding from the amino acid sequence: accurate predictions for protein regions with preferred conformation in the absence of tertiary interactions.
Publication TypeJournal Article
Year of Publication1992
AuthorsRooman, M. J., Kocher J. P., and Wodak S. J.
JournalBiochemistry
Volume31
Issue42
Pagination10226-38
Date Published1992 Oct 27
ISSN0006-2960
KeywordsAmino Acid Sequence, Molecular Sequence Data, Protein Conformation, Protein Folding, Protein Structure, Tertiary, Proteins, Structure-Activity Relationship
Abstract

A recently developed procedure to predict backbone structure from the amino acid sequence [Rooman, M., Kocher, J. P., & Wodak, S. (1991) J. Mol. Biol, 221, 961-979] is fine tuned to identify protein segments, of length 5-15 residues, that adopt well-defined conformations in the absence of tertiary interactions. These segments are obtained by requiring that their predicted lowest energy structures have a sizable energy gap relative to other computed conformations. Applying this procedure to 69 proteins of known structure, we find that regions with largest energy gaps--those having highly preferred conformations--are also the most accurately predicted ones. On the basis of previous findings that such regions correlate well with sites that become structured early during folding, our approach provides the means of identifying such sites in proteins without prior knowledge of the tertiary structure. Furthermore, when predictions are performed so as to ignore the influence of residues flanking each segment along the sequence, a situation akin to excising the considered peptide from the rest of the chain, they offer the possibility of identifying protein segments liable to adopt well-defined conformations on their own. The described approach should have useful applications in experimental and theoretical investigations of protein folding and stability, and aid in designing peptide drugs and vaccines.

Alternate JournalBiochemistry
PubMed ID1420144