TY - JOUR
T1 - Extracting Information on Folding from the Amino Acid Sequence
T2 - Accurate Predictions for Protein Regions with Preferred Conformation in the Absence of Tertiary Interactions
AU - Rooman, Marianne J.
AU - Kocher, Jean Pierre A.
AU - Wodak, Shoshana J.
PY - 1992/2/1
Y1 - 1992/2/1
N2 - 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.
AB - 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.
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U2 - 10.1021/bi00157a009
DO - 10.1021/bi00157a009
M3 - Article
C2 - 1420144
AN - SCOPUS:0026447086
SN - 0006-2960
VL - 31
SP - 10226
EP - 10238
JO - Biochemistry
JF - Biochemistry
IS - 42
ER -