NMR study and molecular dynamics simulations of optimized β-hairpin fragments of protein G

Abstract

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 Gin 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. © 2007 Wiley-Liss, Inc.