EXTRACTING INFORMATION ON FOLDING FROM THE AMINO-ACID-SEQUENCE - ACCURATE PREDICTIONS FOR PROTEIN REGIONS WITH PREFERRED CONFORMATION IN THE ABSENCE OF TERTIARY INTERACTIONS

被引:106
作者
ROOMAN, MJ [1 ]
KOCHER, JPA [1 ]
WODAK, SJ [1 ]
机构
[1] UNIV LIBRE BRUXELLES,UNITE CONFORMAT MACROMOLEC BIOL,CP 160 16,AVE P HEGER,B-1050 BRUSSELS,BELGIUM
关键词
D O I
10.1021/bi00157a009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:10226 / 10238
页数:13
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