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NMR study and molecular dynamics simulations of optimized β‐hairpin fragments of protein G
Author(s) -
Wei Yun,
HuyghuesDespointes Beatrice M. P.,
Tsai Jerry,
Scholtz J. Martin
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21494
Subject(s) - molecular dynamics , peptide , chemistry , biophysics , folding (dsp implementation) , protein folding , protein structure , computational chemistry , biochemistry , biology , electrical engineering , engineering
The stability and structure of several β‐hairpin peptide variants derived from the C‐terminus of the B1 domain of protein G were investigated by a number of experimental and computational techniques. Our analysis shows that the structure and stability of this hairpin can be greatly affected by one or a few simple mutations. For example, removing an unfavorable charge near the N‐terminus of the peptide (Glu42 to Gln or Thr) or optimization of the N‐terminal charge–charge interactions (Gly41 to Lys) both stabilize the peptide, even in water. Furthermore, a simple replacement of a charged residue in the turn (Asp47 to Ala) changes the β‐turn conformation. Finally, we show that the effects of combining these single mutations are additive, suggesting that independent stabilizing interactions can be isolated and evaluated in a simple model system. Our results indicate that the structure and stability of this β‐hairpin peptide can be modulated in numerous ways and thus contributes toward a more complete understanding of this important model β‐hairpin as well as to the folding and stability of larger peptides and proteins. Proteins 2007. © 2007 Wiley‐Liss, Inc.