Premium
β‐Turn propensities as paradigms for the analysis of structural motifs to engineer protein stability
Author(s) -
Ohage Ettore C.,
Graml Werner,
Walter Monika M.,
Steipe Boris,
Steinbacher Stefan
Publication year - 1997
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560060125
Subject(s) - protein stability , protein engineering , protein folding , structural motif , protein structure , structural biology , stability (learning theory) , structural stability , computational biology , chemistry , biology , computer science , genetics , engineering , biochemistry , structural engineering , machine learning , enzyme
The thermodynamic stability of a protein provides an experimental metric for the relationship of protein sequence and native structure. We have investigated an approach based on an analysis of the structural database for stability engineering of an immunoglobulin variable domain. The most frequently occurring residues in specific positions of β‐turn motifs were predicted to increase the folding stability of mutants that were constructed by site‐directed mutagenesis. Even in positions in which different residues are conserved in immunoglobulin sequences, the predictions were confirmed. Frequently, mutants with increased β‐turn propensities display increased folding cooperativities, suggesting pronounced effects on the unfolded state independent of the expected effect on conformational entropy. We conclude that structural motifs with predominantly local interactions can serve as templates with which patterns of sequence preferences can be extracted from the database of protein structures. Such preferences can predict the stability effects of mutations for protein engineering and design.